CHK-336

CHK-336

Names
IUPAC name 2-[5-(cyclopropylmethyl)-3-(4-fluorophenyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid
Identifiers
CAS Number	2743436-86-2
3D model (JSmol)	Interactive image
ChemSpider	129432022
PubChem CID	162358463
UNII	7UP4ZPR62H
InChI InChI=1S/C24H20F2N4O4S2/c25-16-6-4-15(5-7-16)22-17(9-14-3-8-21(18(26)10-14)36(27,33)34)20(11-13-1-2-13)30(29-22)24-28-19(12-35-24)23(31)32/h3-8,10,12-13H,1-2,9,11H2,(H,31,32)(H2,27,33,34) Key: XAHAUTPHLZAEKK-UHFFFAOYSA-N
SMILES NS(=O)(=O)C1=C(F)C=C(CC2=C(CC3CC3)N(N=C2C4=CC=C(F)C=C4)C5=NC(=CS5)C(O)=O)C=C1
Properties
Chemical formula	C24H20F2N4O4S2
Molar mass	530.56 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

CHK-336 is a small molecule lactate dehydrogenase inhibitor developed by Chinook Therapeutics (a Novartis Company). CHK-336 is a first-in-class, orally available, and liver-targeted molecule and is being investigated for the treatment of primary hyperoxaluria. By inhibiting the final and only committed step in hepatic oxalate synthesis, CHK-336 could in principle treat all forms of primary hyperoxaluria.^[1]

In April 2022, a phase 1 clinical trial of CHK-336 was initiated.^[2] This trial was designed to evaluate the safety, tolerability, and pharmacokinetic profile of CHK-336 in healthy volunteers. CHK-336 was found to be generally well-tolerated in single doses up to 500 mg and multiple doses up to 60 mg for 14 days.^[3][4] Pharmacokinetic evaluation supported once-daily dosing, and use of a ¹³C₂-glycolate tracer established proof-of-mechanism that CHK-336 blocks hepatic oxalate production.^[3][4] This clinical trial was paused in April 2023 upon one serious adverse event of anaphylaxis in the 125 mg multiple ascending dose cohort.^[5]