CHZ868

CHZ868
Identifiers
	IUPAC name N-[4-[2-(2,4-difluoroanilino)-1,4-dimethylbenzimidazol-5-yl]oxypyridin-2-yl]acetamide;
CAS Number	1895895-38-1;
PubChem CID	91885989;
ChemSpider	57876249;
ChEBI	CHEBI:90828;
Chemical and physical data
Formula	C22H19F2N5O2
Molar mass	423.424 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C=CC2=C1N=C(N2C)NC3=C(C=C(C=C3)F)F)OC4=CC(=NC=C4)NC(=O)C;
	InChI InChI=1S/C22H19F2N5O2/c1-12-19(31-15-8-9-25-20(11-15)26-13(2)30)7-6-18-21(12)28-22(29(18)3)27-17-5-4-14(23)10-16(17)24/h4-11H,1-3H3,(H,27,28)(H,25,26,30); Key:KQQLBXFPTDVFAJ-UHFFFAOYSA-N;

CHZ868 is a drug which acts as a Janus kinase inhibitor selective for the JAK2 subtype. It was one of the first Janus kinase inhibitors developed, originally for the treatment of leukemia and related blood cancers, and while it did not get approved for clinical use, it is still used for research in the area.^[1]^[2]^[3]^[4]

References

^ Meyer SC, Keller MD, Chiu S, Koppikar P, Guryanova OA, Rapaport F, et al. (July 2015). "CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms". Cancer Cell. 28 (1): 15–28. doi:10.1016/j.ccell.2015.06.006. PMC 4503933. PMID 26175413.
^ Kong X, Sun H, Pan P, Li D, Zhu F, Chang S, et al. (August 2017). "How Does the L884P Mutation Confer Resistance to Type-II Inhibitors of JAK2 Kinase: A Comprehensive Molecular Modeling Study". Scientific Reports. 7 (1): 9088. Bibcode:2017NatSR...7.9088K. doi:10.1038/s41598-017-09586-3. PMC 5567357. PMID 28831147.
^ Nair PC, Piehler J, Tvorogov D, Ross DM, Lopez AF, Gotlib J, Thomas D (September 2023). "Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches". Blood Cancer Discovery. 4 (5): 352–364. doi:10.1158/2643-3230.BCD-22-0189. PMC 10472187. PMID 37498362.
^ Codilupi T, Szybinski J, Arunasalam S, Jungius S, Dunbar AC, Stivala S, et al. (February 2024). "Development of Resistance to Type II JAK2 Inhibitors in MPN Depends on AXL Kinase and Is Targetable". Clinical Cancer Research. 30 (3): 586–599. doi:10.1158/1078-0432.CCR-23-0163. PMC 10831334. PMID 37992313.

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[1] Meyer SC, Keller MD, Chiu S, Koppikar P, Guryanova OA, Rapaport F, et al. (July 2015). "CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms". Cancer Cell. 28 (1): 15–28. doi:10.1016/j.ccell.2015.06.006. PMC 4503933. PMID 26175413.

[2] Kong X, Sun H, Pan P, Li D, Zhu F, Chang S, et al. (August 2017). "How Does the L884P Mutation Confer Resistance to Type-II Inhibitors of JAK2 Kinase: A Comprehensive Molecular Modeling Study". Scientific Reports. 7 (1): 9088. Bibcode:2017NatSR...7.9088K. doi:10.1038/s41598-017-09586-3. PMC 5567357. PMID 28831147.

[3] Nair PC, Piehler J, Tvorogov D, Ross DM, Lopez AF, Gotlib J, Thomas D (September 2023). "Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches". Blood Cancer Discovery. 4 (5): 352–364. doi:10.1158/2643-3230.BCD-22-0189. PMC 10472187. PMID 37498362.

[4] Codilupi T, Szybinski J, Arunasalam S, Jungius S, Dunbar AC, Stivala S, et al. (February 2024). "Development of Resistance to Type II JAK2 Inhibitors in MPN Depends on AXL Kinase and Is Targetable". Clinical Cancer Research. 30 (3): 586–599. doi:10.1158/1078-0432.CCR-23-0163. PMC 10831334. PMID 37992313.

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See also

References