| Identification | Back Directory | [Name]
1H-Pyrazolo[3,4-d]pyriMidin-4-aMine, 1-[trans-4-(4-Methyl-1-piperazinyl)cyclohexyl]-3-(4-phenoxyphenyl)- | [CAS]
330786-01-1 | [Synonyms]
KIN-8194
RLVCBYBGVBOVFV-HZCBDIJESA-N
1H-Pyrazolo[3,4-d]pyriMidin-4-aMine, 1-[trans-4-(4-Methyl-1-piperazinyl)cyclohexyl]-3-(4-phenoxyphenyl)- | [Molecular Formula]
C28H33N7O | [MOL File]
330786-01-1.mol | [Molecular Weight]
483.608 |
| Chemical Properties | Back Directory | [Boiling point ]
681.407±55.00 °C(Press: 760.00 Torr)(predicted) | [density ]
1.341±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
8.202±0.42(predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
KIN-8194 is an orally active dual inhibitor of HCK and BTK, with IC50 values of 0.915 and <0.495 nM, respectively. KIN-8194 impairs growth and integrin-mediated adhesion of BTKi-resistant mantle cell lymphoma (MCL). KIN-8194 overcomes ibrutinib (HY-10997) resistance with a survival benefit in TMD-8 ABC DLBCL xenografted mice[1][2]. | [in vivo]
KIN-8194 (12.5-50 mg/kg, p.o., once time) blocks pHCK and pBTK in a dose-dependent manner in MYD88-mutated TMD-8 ABC DLBCL xenograft mouse model[2].
KIN-8194 (50 mg/kg, p.o., daily, 6 weeks) inhibits tumor growth in MYD88-mutated TMD-8 ABC DLBCL xenograft mouse model[2].
KIN-8194 (30 mg/kg, p.o., daily, 22 days) combined with Venetoclax (HY-15531) prolongs the survival of ibrutinib-resistant BTKCys481Ser TMD-8 cells xenograft mice median survival time[2].
| [References]
[1] Lantermans HC, et al. The dual HCK/BTK inhibitor KIN-8194 impairs growth and integrin-mediated adhesion of BTKi-resistant mantle cell lymphoma. Leukemia. 2024 Mar 7. DOI:10.1038/s41375-024-02207-9
[2] Yang G, et al. The HCK/BTK inhibitor KIN-8194 is active in MYD88-driven lymphomas and overcomes mutated BTKCys481 ibrutinib resistance. Blood. 2021 Nov 18;138(20):1966-1979. DOI:10.1182/blood.2021011405 |
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