KNX-100

Pharmaceutical compound From Wikipedia, the free encyclopedia

KNX-100, also known as synthetic oxytocin-like compound 1 (SOC-1), is a small-molecule oxytocin-like drug or indirect oxytocin receptor modulator acting as an arachidonate 15-lipoxygenase (ALOX15) inhibitor which is under development for the treatment of aggression and agitation in dementia, opioid-related disorders, other substance-related disorders, and behavioral disorders.^[2]^[5]^[6]^[3]^[7]^[1] It is taken orally.^[2]^[3]^[4]^[1]

Other namesKNX100; Synthetic oxytocin-like compound 1; SOC-1; SOC1^[1]

Routes of
administrationOral^[2]^[3]^[4]^[1]

Drug classOxytocin-like drug; Indirect oxytocin receptor modulator; Arachidonate 15-lipoxygenase (ALOX15) inhibitor

ATC code

None

Quick facts Clinical data, Other names ...

KNX-100
Clinical data


Other names	KNX100; Synthetic oxytocin-like compound 1; SOC-1; SOC1^[1]
Routes of administration	Oral^[2]^[3]^[4]^[1]
Drug class	Oxytocin-like drug; Indirect oxytocin receptor modulator; Arachidonate 15-lipoxygenase (ALOX15) inhibitor
ATC code	None
Identifiers
IUPAC name 1-methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine
CAS Number	479234-83-8
PubChem CID	135741977
ChemSpider	16096687
UNII	Y6CLK4BRD4
Chemical and physical data
Formula	C₁₁H₁₂N₄
Molar mass	200.245 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CN1C2=C(CNC3=CC=CC=C3N2)C=N1
InChI InChI=1S/C11H12N4/c1-15-11-8(7-13-15)6-12-9-4-2-3-5-10(9)14-11/h2-5,7,12,14H,6H2,1H3 Key:YAHHFPJGDOWLGU-UHFFFAOYSA-N

Pharmacology

The pharmacodynamics, pharmacokinetics, and toxicity of KNX-100 have been studied.^[6]^[8]^[7]^[9]^[10]^[1]

Pharmacokinetics

KNX-100 has improved pharmacokinetics relative to oxytocin, such as enhanced oral bioavailability, blood–brain barrier permeability, and metabolic stability, and may overcome the pharmacokinetic and efficacy limitations of oxytocin.^[6]^[4]^[7]^[10]^[11]^[1]

Pharmacodynamics

KNX-100 produces oxytocin-like effects, such as pro-social, anti-aggressive, and anti-addictive effects among others, in rodents and monkeys.^[6]^[8]^[9]^[12]^[4]^[13]^[7]^[14]^[11]^[15]^[1] The drug reduced self-administration of methamphetamine in rats by 85%, of cocaine in rhesus monkeys by 90%, and of alcohol in baboons by more than 50%.^[16]^[6]^[12]^[9]^[14]^[1] It is thought that KNX-100 may produce its antiaddictive effects by discounting drug reward in favor of social reward.^[12] In addition to its antiaddictive effects, KNX-100 reduces opioid withdrawal and nicotine withdrawal symptoms in animals.^[17]^[14]^[18]^[19] It appears to act to reduce opioid withdrawal symptoms by suppressing increased dynorphin/κ-opioid receptor signaling in the nucleus accumbens shell.^[18]^[17]^[20]

Unexpectedly, KNX-100 did not show affinity for the oxytocin receptor nor act as an agonist, antagonist, or positive allosteric modulator of the receptor, but nonetheless robustly activates oxytocinergic signaling.^[9]^[8]^[1] In fact, KNX-100 can activate oxytocinergic signaling and cause associated effects to a greater extent than oxytocin itself.^[21]^[1] Screening at more than 100 different receptors and transporters was initially unable to identify the drug's biological target.^[9]^[1] It was suggested that KNX-100 may be acting at an upstream target to indirectly modulate the oxytocin system and increase oxytocin production.^[8]^[6] Subsequently, KNX-100 was said by its developers to have a novel undisclosed mechanism of action.^[18]^[10] In January 2026, it was disclosed that KNX-100 acts as an inhibitor of arachidonate 15-lipoxygenase (ALOX15), a lipoxygenase enzyme involved in the metabolism of polyunsaturated fatty acids (PUFAs).^[22]

Chemistry

KNX-100 is a synthetic small molecule and peptide fragment of the oxytocin system.^[6]^[7]^[23] Its chemical structure has been disclosed by its developers in a patent.^[1] The chemical synthesis of KNX-100 has been described.^[1]^[24] The small-molecule oxytocin receptor agonist LIT-001 is a derivative of KNX-100.^[25]

History

KNX-100 was first described in the scientific literature by 2012.^[8]^[7]^[9] It was originated at the University of Sydney by Iain McGregor and Michael Bowen and colleagues and is under development by Kinoxis Therapeutics in partnership with Boehringer Ingelheim.^[2]^[6]^[3]^[26] In 2018, it was reported that KNX-100 had been under development for more than a decade.^[12] The drug was identified via a phenotypic screen of compounds derived from a fragment-based drug discovery system targeting the oxytocin system.^[6]^[10]^[11]^[23] In January 2026, it was disclosed that KNX-100's mechanism of action is inhibition of the enzyme arachidonate 15-lipoxygenase (ALOX15).^[22]

Research

As of August 2025, KNX-100 is in phase 2 clinical trials for treatment of agitation and aggression in dementia, phase 1 trials for opioid-related disorders and substance-related disorders, and the preclinical research stage of development for behavioral disorders.^[2] Phase 1 trials were first planned for 2019.^[6] Several clinical trials of KNX-100 have been registered with details provided.^[27]^[28]^[29] In addition to the preceding indications, there is also interest in KNX-100 for other potential applications like treatment of social anxiety, other types of addiction besides substance addiction like gambling, and pain, among others.^[6]^[22] Besides KNX-100, Kinoxis Therapeutics also has selective oxytocin receptor partial agonists like its KNX-200 series and oxytocin receptor positive allosteric modulators like its KNX-300/400 series in its developmental pipeline.^[26]^[30]^[31]^[32]^[33]

References

[1]
McGregor IS, Kassiou M, Bowen MT, Hicks C, Jorgensen W (7 May 2021). "Therapeutic compounds and compositions for treating social disorders and substance use disorders". Google Patents. Kinoxis Therapeutics Pty Ltd. One example salt of Formula (I) is the hydrochloride salt of: structure] The hydrochloride salt: [structure] is utilised in the following examples and has been given the code SOС-1. [...] Fos immunohistochemistry was used to identify the neural "signature" of SOC-1 (5 mg/kg) in rat brain relative to injections of peripheral oxytocin (OT) (1 mg/kg). Results are shown in Table 4. SOC-1 produces a similar overall pattern of neural activation and behavioural effects as OT. However, the effects are much larger and additional areas are activated by SOC-1 that are implicated in the regulation of social behaviour (e.g. lateral septum, medial preoptic area and supraoptic nucleus). SOC-1 produces powerful activation of OT-containing neurons in both the supraoptic (FIG. 6: (A)=vehicle; (B)=oxytocin; and (C)=SOC-1) and paraventricular nucleus of the hypothalamus. SOC-1 (5 mg/kg) given to male Wistar rats strongly activates Fos expression in the oxytocin-positive cells in the supraoptic nucleus of the hypothalamus (SON). SOC-1 is substantially more effective at activating these oxytocin-containing cells in the SON than 1 mg/kg of oxytocin (intraperitoneal injection). Remarkably, however, SOC-1 does not show affnity for the orthosteric binding sites on the oxytocin receptor (OTR) (human OT receptor, IC50 (nM) against [3H]OT=>10000). Furthermore, examination of IP1 signalling on OTR HEK cells has revealed that SOC-1 is not an agonist or antagonist at OTRs, nor a positive allosteric modulator of the OTR. Nor does SOC-1 show any affinity for the orthosteric binding sites of AVP receptors (V1A, V1B or V2) (e.g. human V1a receptor, IC50 (nM) against IP1 signalling on V1aR HEK cells revealed that SOC-1 is not an agonist or positive allosteric modulator of V1aRs, but showed weak antagonist activity at these receptors. Comprehensive screening of affinity for the orthosteric binding sites for numerous receptors from the Psychoactive Drug Screening Program (PDSP) have failed as yet to identify a target, despite the powerful OT-like behavioural effects of the compound evident in vivo and the clear activation of brain OT systems evident from our Fos data. In the PDSP, SOC-1 had no notable affnity for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5a, 5-HT6, 5-HT7, Alpha1B, Alpha1D, Alpha2A, Alpha2B, Alpha2C, Beta1, Beta2, Beta3, BZP Rat Brain Site, D1, D2, D3, D4, D5, DAT, DOR, GABAA, H1, H2, H3, KOR, M1, M2, M3, M4, M5, MOR, NET, PBR, SERT, Sigma 1 and Sigma 2 receptors. Examination of signalling using rat hypothalamic neurons showed that SOC-1 did not alter IP1 levels and did not reliably alter Ca2+ levels. However, SOC-1 was able to decrease basal cAMP, but did not reliably decrease forskolin-stimulated cAMP. All of this suggests that it may either be working on a Gs-coupled receptor as an inverse agonist, or as a Gi-coupled receptor agonist.
[2]
"KNX 100". AdisInsight. 4 August 2025. Retrieved 13 January 2026.
[3]
"KNX-100 by Kinoxis Therapeutics for Opium (Opioid) Addiction: Likelihood of Approval". Pharmaceutical Technology. 9 September 2024. KNX-100 overview: KNX-100 is under development for the treatment of alcohol addiction, drug (methamphetamine, cocaine and opioid) addiction, aggression and agitation in dementia. It is administered through oral route. The drug candidate targets non-peptide oxytocin receptor (OTR).
[4]
"Combatting addiction with 'the love hormone'". sponsored.chronicle.com. 3 November 2021. Retrieved 13 January 2026. [(KNX-100)], which was discovered at the University of Sydney, mimics the anti-addictive and pro-social effects of oxytocin, as well as a number of its effects in the brain, but overcomes the limitations of administering oxytocin itself. So promising is KNX100, Associate Professor Bowen co-founded a spinout company, Kinoxis Therapeutics, in 2018 to fully focus the research. KNX100 is being developed by Kinoxis to treat opioid-use disorder as well as a range of other substance use disorders and central nervous system disorders. In collaboration with the University of Sydney, Kinoxis was awarded a grant of up to $US.4.6 million by the US National Institutes of Health – recognition of KNX100's potential to successfully manage opioid withdrawal symptoms and help curb the opioid crisis. The first ever human clinical trial with KNX100 is scheduled to commence in early 2022. That will make it the only novel compound in clinical development for opioid use disorder anywhere in the world.
[5]
"Delving into the Latest Updates on KNX-100 with Synapse". Synapse. 27 December 2025. Retrieved 13 January 2026.
[6]
Klein A (31 January 2018). "A Helping Hand / The Love Drug That Could Draw People Away From Any Addiction". New Scientist. doi:10.1016/S0262-4079(18)30221-5. Growing impatient, McGregor suggested to Jorgensen that they test these three precursor fragments in rats "just for the hell of it", says Bowen. The first two fragments did nothing. But after they injected the third one, they found the rats became more social, showing an increased preference for spending time with other rats rather than objects, and even cuddling up to rats they had never met before. "Bingo. That was when we thought it must be activating the oxytocin system," says Bowen. [...] To confirm this, they looked at what was happening in the rats' brains. Sure enough, they found the fragment was strongly activating the brain's two major oxytocin-producing factories. [...] Since then, the team has tested this small molecule – named synthetic oxytocin-like compound 1 (SOC-1) – in rats addicted to methamphetamine, rhesus monkeys hooked on cocaine and baboons with an alcohol habit. The results have been "nothing short of incredible", says Bowen. For example, when SOC-1 was injected into the rats, their motivation to consume methamphetamine – measured by how many times they pressed a lever to get a hit – dropped by more than 85 per cent. Similarly, with the rhesus monkeys, their interest in self-administering cocaine fell by 90 per cent. In other words, instead of pressing a lever almost 350 times to get one intravenous shot of cocaine, the monkeys gave up after 35 goes. Impressively, the molecule also seemed to prevent relapse, one of the biggest barriers to recovery in those with substance use disorders. SOC-1 seems to weaken the power of these triggers. In one experiment, rats were trained to push a lever to self-administer methamphetamine. Once they were addicted, the set-up was changed so the lever no longer released any drug. Eventually, the rats gave up pressing it – this was the "rehab" phase. Butthen they were given one tiny dose of methamphetamine. Immediately, they switched into a frenzied state, hammering the lever over 120 times during a 2-hour period to try to get another hit. In contrast, those treated with SOC-1 just before receiving this prime barely touched the lever. According to McGregor, the effects of SOC-1 could be long-lasting. [...] The big question the team is now trying to answer is: how exactly does SOC-1 work? Their research so far suggests it stimulates a rush of oxytocin that recalibrates the brain's focus towards social engagement. [...] Phase I clinical trials with a pill version of SOC-1 are planned for 2019. First, they will lookat treating people who have drug addictions, but one day it might be possible to inoculate teenagers against future drug addictions. But will it have side effects? In lab animals, SOC-1 didn't show any signs of toxicity and didn't cause weight changes or problematic behaviour. Importantly, SOC-1 isn't addictive itself: rats given the opportunity to self-administer showed no interest in doing so. [...] "Oxytocin doesn't seem to be rewarding in and of itself," says Bowen. "It's more subtle. It might just make you want to hang out with your friends instead of pursuing a drug." This makes SOC-1 different to replacement therapies like methadone, which can help people get off heroin and other opioids, but is addictive itself. [...] McGregor and Bowen are now looking into other possible applications of SOC-1, like treating social anxiety.It might also work for other types of addition, like gambling, which has a similar effect on the brain to drugs.{{cite journal}}: CS1 maint: deprecated archival service (link)
[7]
Baracz S, Everett N, Bowen M, Kassiou M, Cornish J, McGregor I (June 2016). A novel oxytocin-like compound reduces motivation to self-administer methamphetamine and relapse to methamphetamine seeking in rats (PDF). International Behavioral Neuroscience Society (IBNS), Annual Meeting Program and Abstracts Budapest, Hungary June 7–11, 2016. The psychostimulant methamphetamine (METH) is an addictive illicit drug. The neuropeptide oxytocin has been shown to robustly reduce METH-related reward and abuse in rodents. However, its poor permeability of the blood brain barrier and limited oral bioavailability impacts on its therapeutic potential. The recent development of synthetic oxytocin-like compound -1 (SOC-1), a small molecule with enhanced blood brain barrier penetration and oral bioavailability with oxytocin-like effects on enhancing social behaviours, is a promising therapeutic alternative. The ability of SOC-1 to reduce METH abuse and relapse, although, had not yet been investigated. The aim of the study was to investigate whether SOC-1 administration reduces motivation for METH intake and drug-primed reinstatement to METH-seeking behaviour. Male Sprague Dawley rats with implanted jugular vein catheters were initially trained to self-administer METH (0.1 mg/kg/infusion) under a fixed ratio 1 schedule of reinforcement. Rats then advanced to a progressive ratio (PR) reinforcement schedule to examine the effect of SOC-1 (0, 1.25, 2.5, 5, and 10 mg/kg) intraperitoneal (ip) administration on motivation for METH taking, or underwent testing of SOC-1 (0, 2.5, 5, and 10 mg/kg; ip) effects on drug-primed reinstatement of METH seeking following extinction. Our results showed that SOC-1 administration reduced PR responding for METH (5mg/kg and 10mg/kg doses) and relapse to METH-seeking behaviour (all tested doses). Overall, these findings demonstrate that SOC-1 has similar effects to oxytocin on reducing methamphetamine-taking and -seeking behaviours and provides further support for its application as a therapeutic tool. This work was supported by an NHMRC grant 1088711.
[8]
Hicks C, Bowen MT, Ramos L, Jorgensen W, Kassiou M, Hunt GE, et al. (June 2012). In Vivo Characterisation of SOC-1: A Novel Prosocial Compound (PDF). International Behavioral Neuroscience Society, Annual Meeting Program and Abstracts, Kailua-Kona, Hawaii, USA June 5–10, 2012, Abstracts of the International Behavioral Neuroscience Society, Volume 21, June 2012. Psychiatric disorders (e.g. autism) may benefit through the development of compounds that act to stimulate social behaviour. Accordingly, our drug discovery program is focused on compounds that modulate brain oxytocin, vasopressin and neurosteroid systems to facilitate social behaviour in rodents. SOC-1 evolved from our program producing non-peptide compounds that interact with brain oxytocin receptors. SOC-1 (5 mg/kg, IP) caused similar brain Fos expression to the non-peptide oxytocin agonist/vasopressin antagonist WAY 267,464 (100 mg/kg, IP) and oxytocin itself (1 mg/kg, IP), with pronounced expression in the supraoptic and paraventricular hypothalamic nuclei, lateral parabrachial nucleus and nucleus of the solitary tract, and greater activation in the lateral septal nucleus and medial preoptic area. In the 'classic' social interaction test, SOC-1 (5 mg/kg) increased the time rats spent lying adjacent to a novel conspecific. The same dose also increased the time rats spent interacting with a caged live rat, relative to a caged dummy rat, in a social preference paradigm. These prosocial effects appeared to be independent of a general anxiolytic effect as SOC-1 failed to affect behaviour on the elevated plus-maze. Biotelemetry studies in rats showed that SOC-1 (5 mg/kg) had a strong hypothermic effect, similar to oxytocin (1 mg/kg), but unlike oxytocin did not cause reductions in heart rate. SOC-1 also reversed the hyperthermia seen during acute social interaction. Pretreatment with an oxytocin receptor antagonist (Pfizer Compound 25, 10 mg/kg, IP), vasopressin 1a receptor antagonist (SR 49059, 10 mg/kg, IP) or a benzodiazepine antagonist (flumazenil, 10 mg/kg, IP) did not prevent the hypothermic effects of SOC-1. Ongoing receptor binding studies suggest that SOC-1 actually has low affinity for oxytocin and vasopressin receptors and may therefore be acting on an upstream target to indirectly modulate these systems. Overall, SOC-1 is a novel prosocial compound with an oxytocin-like profile of brain activation and body temperature. It represents a novel research tool for examining in vivo the mechanisms and neural circuitry underlying social behaviour.
[9]
Iain McGregor (October 2017). Serendipity and the Hard Slog: An Insiders Account of the Discovery and Development of a Novel Therapeutic for Treating Addiction and Social Deficits (PDF). Biological Psychiatry Australia 7th Annual Scientific Meeting, Wollongong Sunday 29 — Tuesday 31 October 2017, Abstract Book. The past few years have seen increasing interest in the neuropeptide oxytocin as a novel and effective intervention for addictive behaviour and for psychiatric disorders that feature social withdrawal as a central feature (e.g. autism). Early studies in laboratory animals showed the capacity of oxytocin to increase prosocial behaviours and to reduce methamphetamine, cocaine and alcohol self-administration and withdrawal symptoms. However, oxytocin itself is unlikely to ever become a mainstream therapeutic due to its poor brain penetration and lack of oral bioavailability. Investigation of non-peptide small molecule oxytocin-like compounds by our group lead to the serendipitous discovery of Synthetic Oxytocin-Like-Compound 1 (SOC-1), a novel compound that stimulates brain oxytocin circuitry and has dramatic prosocial and anti-addiction effects in animal models. SOC-1 reduces intravenous methamphetamine self-administration and reinstatement of methamphetamine seeking behavior in rats, reduces cocaine self-administration in rhesus monkeys, and alcohol self-administration in baboons. SOC-1 shows favourable pharmacokinetics and a very promising toxicity profile, and further testing is being currently undertaken in the USA and Australia to enable fast tracking of Phase 1 human clinical trials. The mode of action of SOC-I remains something of a mystery: it stimulates magnocellular oxytocin-containing neurons in the hypothalamus but does not show affinity for more than 100 different receptors and transporters that have been screened, including the oxytocin receptor. Microarray and activity-based proteomic profiling are currently being conducted to better elucidate the actions of SOC-1 on the central nervous system.
[10]
Nick Everett (November 2024). Symposium 5 - Icy Insights: Facilitating Dialogue to Advance the Treatment of Methamphetamine Use Disorder in Australia: Dr Nick Everett, The University of Sydney and Kinoxis Therapeutics (PDF). The 14th Biological Psychiatry Australia Scientific Meeting 3rd – 5th November 2024. Abstract: Despite rising rates of methamphetamine addiction globally, there are no approved pharmacotherapies. While psychosocial interventions are effective for some, they are inaccessible for many. Therefore, novel pharmacotherapies are urgently needed. KNX100 is a novel molecular entity discovered through a phenotypic screen for positive effects on social behaviour in rodents, with a novel undisclosed mechanism of action. KNX100 is orally bioavailable, with peripheral administration having a good plasma and brain half-life and resulting in a high brain free concentration. KNX100 has undergone safety, tolerability, and pharmacokinetic testing in Phase 1 clinical trial under an FDA IND for mitigation of opioid withdrawal symptoms. However, preclinical experiments in both rodents and non-human primates suggest KNX100 may also have utility as a novel therapeutic for stimulant use disorder. This talk will present the rationale for pursuing KNX100 for methamphetamine use disorder. The data to be presented comes primarily from experiments in rat models of methamphetamine intravenous self-administration, utilising models of motivated intake (progressive ratio, behavioural economics), relapse-like behaviour (drug-primed and cue-primed reinstatement), methamphetamine preference over social reward, and methamphetamine sensitisation. These data have translated to similar effects in non-human primate models of cocaine self-administration. Importantly, we will show that KNX100 is not inherently sedating, rewarding, reinforcing, or aversive. We will also present the plan for translation of KNX100's effects to Phase 2 clinical trials in patients with methamphetamine use disorder. KNX100 is the first novel chemical entity developed and tested clinically in Australia for this indication.
[11]
Michael Bowen (December 2019). Rebalancing the addicted brain: prosocial compounds for treating substance use disorders (PDF). Australasian Neuroscience Society (ANS) 2019 Symposium Abstracts. Through a phenotypic drug discovery program we discovered a novel small-molecule, KNX100, with powerful prosocial and anti-addictive effects in preclinical models. KNX100 has excellent oral bioavailability, readily enters the brain and a long half-life, overcoming the substantial pharmacokinetic challenges presented by oxytocin. Peripherally administered KNX100 increased social preference and social interaction in rats and restored normal social behaviour in a mouse model of autism. Across rodent and non-human primate models KNX100 has shown considerable promise for treating opioid, nicotine, alcohol and stimulant use disorders. Importantly, KNX100 itself does not appear to have abuse liability. In initial preclinical safety studies KNX100 was well-tolerated with a wide therapeutic window. KNX100 is now being developed by a University of Sydney spinout company, Kinoxis Therapeutics.
[12]
Rogers G (17 March 2018). "The pill that could soon help to beat drug and alcohol addiction 'epidemic'". 9News. Retrieved 13 January 2026.
[13]
Lin J (9 May 2023). "Boehringer, Kinoxis Ink $181 Million Pact To Target Oxytocin Receptors". GeneOnline News -. Retrieved 13 January 2026. Kinoxis' lead compound, KNX100, is currently enrolling patients in a Phase 1 trial for the management of opioid withdrawal symptoms. According to Kinoxis, KNX100 has shown promising preclinical results in animal models of cocaine, methamphetamine, nicotine, and alcohol use disorders, as well as models of agitation and aggression. The drug has drawn attention from the US National Institutes of Health Helping to End Addiction Long-Term, or the NIH HEAL Initiative, which awarded $4.6 million over a four year span to Kinoxis to advance its preclinical and clinical development.
[14]
McGregor IS, Bowen MT, Foltin R, Baracz SJ, Cornish JL (2018). "Speaker Abstracts: Development of Small Molecule Oxytocin Ligands for Alcohol Dependence and Drug Addiction". Alcoholism: Clinical and Experimental Research. 42 (S2). doi:10.1111/acer.13834. ISSN 0145-6008. In 2010 our group reported that systemic injections of oxytocin inhibited both beer consumption and intravenous methamphetamine self-administration in rats. Our subsequent research documented a long-lasting inhibition of addictive behaviours as a result of brief oxytocin exposure. These results and others have led to substantial clinical interest in intranasal oxytocin as a therapeutic for addictions. However, our own (unpublished) study of intranasal oxytocin in problem drinkers found only modest effects, most likely due to the relatively poor central penetration and bioavailability of oxytocin. Consequently, we have developed a range of small molecules that stimulate central oxytocin circuits. Our lead candidate, SOC-1, has remarkable effects in animal models of addiction. These include dose-dependent reductions in methamphetamine self-administration in rats and reduced prime-induced reinstatement of methamphetamine-seeking. In primate models, SOC-1 (2–4 mg/kg, IM) decreased cocaine self-administration and decreased operant alcohol self-administration in baboons at a dose of 6 mg/kg (P.O.). SOC-1 also prevented a range of nicotine withdrawal symptoms in mice. In addition, SOC-1 has powerful prosocial effects in animal models of autism and in the social interaction test, while being devoid of addictive properties itself. Our current activities are aimed at fast-tracking the passage of SOC-1 into the clinic.
[15]
Salthouse T, Assereh N, Lee T, Wilson B, Tan O, Badolato C, et al. (18 August 2025). "696. Whole Brain Activity Mapping of the Effects of a Novel Small Molecule on Chronic Social Isolation Induced Aggression in Mice". International Journal of Neuropsychopharmacology. 28 (Supplement_2): ii56–ii57. doi:10.1093/ijnp/pyaf052.113. ISSN 1461-1457. PMC 12359352. KNX100 is a novel, prosocial compound that has been shown to reduce aggression in preclinical models. [...] KNX100 and risperidone significantly inhibited hyperaggressive behaviour in chronically socially isolated mice. KNX100 treatment significantly normalised or partially normalised activity associated with aggression in over 100 regions. This included subregions of the hippocampus, amygdala, hypothalamus, thalamus, frontal cortex, basal ganglia, basal forebrain, and midbrain. [...] Distinct activity patterns were associated with the anti-aggressive effects of KNX100 and risperidone. KNX100 treatment was associated with circuits heavily implicated in threat detection, emotional regulation, behavioral inhibition, and sensory integration. In contrast, risperidone acted primarily on regions involved in motor control, arousal, and sensory gating. Interestingly, while both compounds normalised aggressive behaviour, KNX100 is efficacious at doses that have no effects on gross locomotor activity, whereas risperidone modulates aggression at doses that have sedative-like effects. The findings of the present study provide important insights into the differing neural substrates of KNX100 and risperidone effects on aggression and suggest KNX100 may act more through circuits more specifically involved in emotional regulation and aggression.
[16]
"Tableta ljubavi mogla bi izliječiti sve ovisnosti" [A love pill could cure all addictions]. Klubikon (in Croatian). 13 February 2018. [Translated:] In some studies, the effects of oxytocin have been tested on humans, but in small amounts for safety reasons, but the desired effect was not achieved because large molecules of this compound have difficulty passing from the blood to the brain. In an attempt to solve the problem, McGregor and Michael Bowen, with the help of chemists from the University of Sydney, set out to find a molecule that mimics the effects of oxytocin, and which can easily pass from the blood to the brain. They called the molecule SOC-1 (synthetic oxytocin-like compound 1), and its action developed sociability in rats, while reducing their addiction to amphetamine by between 85% and 90%. With equal success, cocaine-addicted monkeys and alcoholic baboons gave up their addictions.
[17]
Everett NA, Scicluna RL, Guy GN, Wilson BB, Bowen MT (June 2021). Discovery of the neural mechanisms of action of a novel treatment for opioid withdrawal (PDF). IBNS 30th Annual Meeting June 1–5, 2021 Puerto Vallarta, Mexico, Poster Abstracts. Opioid misuse is an escalating crisis accounting for 3 deaths per day in Australia and is now the #1 cause of preventable deaths in the USA. Repeated use of the prescription opioid oxycodone rapidly produces dependence, whereby when use is ceased, profound withdrawal symptoms are experienced. This withdrawal syndrome can be relieved by taking the opioid again, causing the individual to lose control over their opioid use, which may result in difficult to treat opioid use disorder. It is essential to treat withdrawal symptoms before this cycle begins. Unfortunately, there are few effective therapies for opioid withdrawal. We have developed a novel small molecule, KNX100, which potently reduces opioid withdrawal symptoms in mice exposed to naloxone-precipitated withdrawal after 8 days of oxycodone injections (twice-daily, increasing doses from 9 to 33 mg/kg). Our goal was to determine KNX100's mechanism of action in the brain. We first conducted whole-brain analysis of neuronal activity using cFos immunofluorescence, to identify regions where KNX100 reduced withdrawal-induced activity. This identified the nucleus accumbens shell (NAcSh), which is a key driver of opioid withdrawal. Next, we used fibre photometric measurement of jGCaMP7s-expressing cells in the NAcSh and discovered that withdrawal-induced jumping was temporally associated with increases in NAcSh activity, and that KNX100 reduced this jump-related activity, as well as reducing elevated baseline and maximal NAcSh activity during withdrawal, demonstrating a likely causal relationship between NAcSh activity and withdrawal-jumps. We then used chemogenetics to inhibit the NAcSh, which was sufficient to reduce withdrawal-induced jumping. Last, we injected KNX100 directly into the NAcSh, at a free drug concentration which is achieved in the NAcSh after systemic KNX100 dosing, which recapitulated the effects of chemogenetic NAcSh inhibition. Together, these data strongly indicate that KNX100 acts via the NAcSh to reduce opioid withdrawal symptoms. Future studies will characterise the cell types which KNX100 interacts with to reduce opioid withdrawal. This work was funded by a research contract with Kinoxis Therapeutics Pty Ltd, and by the National Institute On Drug Abuse of the National Institutes of Health.
[18]
Scicluna R, Doolan TM, Lynch E, Everett N, Bowen M (2023). "A Novel Clinical-stage Small Molecule Targeting the 'Dark Side' of Opioid Addiction". The Journal of Pharmacology and Experimental Therapeutics. 385: 168. doi:10.1124/jpet.122.262620. KNX100 is a novel, clinical stage small molecule being developed for the treatment of opioid use disorder. KNX100 has an undisclosed pharmacological mechanism of action but has been shown to act in the nucleus accumbens shell to reduce neuronal hyperexcitability and signalling in the pDYN/DYN/KOR receptor pathway during opioid withdrawal in mice, demonstrating highly disease-relevant neural and molecular actions. Moreover, KNX100 reduced the negative affective symptoms of acute naloxone-precipitated oxycodone withdrawal and inhibited the acquisition of withdrawal-induced conditioned-place aversion in mice. Here, the effects of KNX100 on irritability during spontaneous oxycodone withdrawal and cue-induced reinstatement of oxycodone-seeking during abstinence were examined in rats. [...] KNX100 treatment significantly reduced withdrawal-induced irritability-like behaviour, but not wet dog shakes, in male and female rats. KNX100 markedly inhibited cue-induced reinstatement of drug seeking 15 days into abstinence. These data further indicate KNX100 may alleviate the negative psychological state that emerges during withdrawal and persists into abstinence that contributes to drug craving and relapse and suggest KNX100 may be a viable therapeutic for alleviating the negative affective aspects of acute withdrawal and promoting abstinence.
[19]
Rhianne Scicluna (2024). Novel Pharmacotherapeutics for Opioid Addiction (PhD thesis). The University of Sydney. hdl:2123/32544. Additionally, it assesses the clinical stage therapeutic, KNX100, for opioid use disorder, utilising rat self-administration models. [...] Moreover, the thesis demonstrates the potential of KNX100 in alleviating negative affective withdrawal symptoms and reducing craving, crucial factors contributing to relapse.
[20]
Salthouse T, Everett N, Guy G, Wilson B, Bowen M (October 2023). Understanding the role of dynorphin in the therapeutic effects of KNX100, a novel clinical stage molecule in development for the treatment of opioid withdrawal (PDF). Biological Psychiatry Australia 2023, Proceedings of the Biological Psychiatry Australia Scientific Meeting 2023, The 13th Biological Psychiatry Australia Scientific Meeting 25 – 27th October 2023.
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Jennifer Horton (3 April 2017). "Hugs not drugs: the USyd researchers developing addiction treatment – Honi Soit". Honi Soit – News, culture, comedy, opinion, satire, and more since 1929. It all sounds too good to be true. And it is… sort of. Oxytocin cannot be administered orally, and in clinical trials where the drug is administered intranasal, the effects were modest at best (most likely due to the small amount of the drug that actually reaches the brain). The solution, Bowen tells us, is a synthetic compound currently in development at USyd. SOC-1 (or Synthetic Oxytocin-like Compound 1) is a pill that works by activating oxytocin neurons in the brain. In fact, the compound has more of an effect than natural oxytocin–activating up to 33% of neurons while oxytocin itself activates only 13.5%. If all goes well, it will still be six to eight years before SOC-1 is available on the pharmaceutical market.
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Michael Bowen, Kinoxis Therapeutics (11 January 2026). Developing Novel ALOX15 Inhibitors for Dementia and Pain, High-Need CNS Indications. Sachs Associates 9th Annual Neuroscience Innovation Forum for Business Development, Licensing & Investment, 11th January 2026, Marines' Memorial Club, San Francisco, USA.
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"Advancing KNX100 for the treatment of opioid withdrawal: preclinical efficacy and toxicology, and a phase 1 clinical program". RePORTER. U.S. National Institutes of Health. 5UH3DA048743-03. Retrieved 13 January 2026. Kinoxis Therapeutics Pty Ltd is an Australian based company that has licensed intellectual property from the University of Sydney, including several candidates for the treatment of substance use disorders. We have developed a novel small molecule lead, KNX100, [...] KNX100 was discovered from a phenotypic screen of compounds derived from a fragment-based drug discovery program targeting the brain oxytocin system. KNX100 has a favorable pharmacokinetic and safety profile in testing thus far. To date, KNX100 has undergone testing for efficacy signals in two rodent and two non-human primate species, with testing taking place across multiple laboratories including National Institute on Drug Abuse (NIDA) commissioned laboratories under the NIDA Medications Development Program. [...]
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Spotlight Showcases: Kinoxis Therapeutics Pty Ltd. 5th Annual Neruoscience Innovation Forum for Business Development, Licensing & Investment 22nd–23rd March 2022, Digital Conference. March 2022. Kinoxis' lead candidate (KNX100) is being developed for the mitigation of opioid withdrawal symptoms. KNX100 has a novel, undisclosed mechanism of action and a Phase I clinical trial has commenced under a US IND. The company is also exploring other indications for its lead compound, KNX100, as promising preclinical results have been achieved in animal models of cocaine, methamphetamine, nicotine, and alcohol use disorders, as well as models of agitation and aggression. [...] Kinoxis' second series of compounds target the oxytocin receptor, through either selective partial agonism or positive allosteric modulation. The brain oxytocin system has been identified as perhaps the most important molecular target for regulating social behaviour and is therefore a major target of interest for treating a wide range of mental disorders. The development of these compounds will be focused on treating conditions that feature social dysfunction as a core symptom, such as neurodevelopmental disorders (including autism spectrum disorder), social anxiety disorder, dementia (including Alzheimer's disease), PTSD and schizophrenia. The KNX200 series of oxytocin receptor partial agonists are undergoing candidate selection stage using several pre-clinical animal disease models (Alzheimer's, PTSD, ASD) and the KNX300/400 series of oxytocin receptor positive allosteric modulators are undergoing lead optimisation.
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https://kinoxistherapeutics.com/wp-content/uploads/2021/04/Kinoxis_Fact_Sheet.pdf
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US 2020/0000823A1, Kassiou M, Jorgensen W, Werry E, Reekie T, Bowen M, McGregor I, "Non-peptide oxytocin receptor agonists", issued 8 November 2022, assigned to Kinoxis Therapeutics Pty Ltd.