ACBI3

ACBI3
Identifiers
	IUPAC name (2S,4R)-1-[(2S)-2-[4-[4-[(3S)-4-[4-[5-[(4S)-2-amino-3-cyano-4-methyl-6,7-dihydro-5H-1-benzothiophen-4-yl]-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]-3-methyl-1,4-diazepan-1-yl]butoxy]triazol-1-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide;
CAS Number	2938169-76-5;
PubChem CID	169449364;
ChemSpider	129422922;
Chemical and physical data
Formula	C50H62N14O6S2
Molar mass	1019.26 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H]1CN(CCCN1C2=NC=CC(=N2)C3=NOC(=N3)[C@]4(CCCC5=C4C(=C(S5)N)C#N)C)CCCCOC6=CN(N=N6)[C@@H](C(C)C)C(=O)N7C[C@@H](C[C@H]7C(=O)N[C@@H](CO)C8=CC=C(C=C8)C9=C(N=CS9)C)O;
	InChI InChI=1S/C50H62N14O6S2/c1-29(2)42(47(68)63-25-34(66)22-38(63)46(67)55-37(27-65)32-11-13-33(14-12-32)43-31(4)54-28-71-43)64-26-40(58-60-64)69-21-7-6-18-61-19-9-20-62(30(3)24-61)49-53-17-15-36(56-49)45-57-48(70-59-45)50(5)16-8-10-39-41(50)35(23-51)44(52)72-39/h11-15,17,26,28-30,34,37-38,42,65-66H,6-10,16,18-22,24-25,27,52H2,1-5H3,(H,55,67)/t30-,34+,37-,38-,42-,50-/m0/s1; Key:DQRZNYPHOWVXPQ-YDUPODKQSA-N;

ACBI3 is an experimental anticancer drug which is one of the first examples of a proteolysis targeting chimera (PROTAC) against the protein KRAS.

CAS Number

2938169-76-5

PubChem CID

169449364

ChemSpider

129422922

FormulaC₅₀H₆₂N₁₄O₆S₂

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Being a PROTAC, it is a bifunctional molecule with two halves joined by a linker; one half binds to its target, KRAS which is a key driver in certain types of cancer, while the other half binds E3 ligase which triggers the cell's natural protein degradation mechanisms. This causes the KRAS protein to be degraded.

In early stage testing, it was able to target 13 of the 17 most common mutated forms of KRAS found in cancer cells, allowing selective targeting of a wide range of cancer types. While this particular molecule is still at an early developmental stage, it is an important proof of concept that KRAS can be targeted with a PROTAC.^[1]^[2]^[3]^[4]

[1]

[2]

[3]

[4]

ACBI3

See also

References

Related Articles

Identifiers

IUPAC name (2S,4R)-1-[(2S)-2-[4-[4-[(3S)-4-[4-[5-[(4S)-2-amino-3-cyano-4-methyl-6,7-dihydro-5H-1-benzothiophen-4-yl]-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]-3-methyl-1,4-diazepan-1-yl]butoxy]triazol-1-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
CAS Number	2938169-76-5
PubChem CID	169449364
ChemSpider	129422922
Chemical and physical data
Formula	C₅₀H₆₂N₁₄O₆S₂
Molar mass	1019.26 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C[C@H]1CN(CCCN1C2=NC=CC(=N2)C3=NOC(=N3)[C@]4(CCCC5=C4C(=C(S5)N)C#N)C)CCCCOC6=CN(N=N6)[C@@H](C(C)C)C(=O)N7C[C@@H](C[C@H]7C(=O)N[C@@H](CO)C8=CC=C(C=C8)C9=C(N=CS9)C)O
InChI InChI=1S/C50H62N14O6S2/c1-29(2)42(47(68)63-25-34(66)22-38(63)46(67)55-37(27-65)32-11-13-33(14-12-32)43-31(4)54-28-71-43)64-26-40(58-60-64)69-21-7-6-18-61-19-9-20-62(30(3)24-61)49-53-17-15-36(56-49)45-57-48(70-59-45)50(5)16-8-10-39-41(50)35(23-51)44(52)72-39/h11-15,17,26,28-30,34,37-38,42,65-66H,6-10,16,18-22,24-25,27,52H2,1-5H3,(H,55,67)/t30-,34+,37-,38-,42-,50-/m0/s1 Key:DQRZNYPHOWVXPQ-YDUPODKQSA-N