Trilaciclib (hydrochloride)

Trilaciclib is an inhibitor of cyclin-dependent kinase 4 (Cdk4)/cyclin D1 and Cdk6/cyclin D3 (IC50s = 1 and 4 nM, respectively). It is selective for Cdk4/cyclin D1 and Cdk6/cyclin D3 over Cdk2/cyclin A, Cdk2/cyclin E, Cdk5/p25, Cdk5/p35, Cdk7/cyclin H/Mat1, and Cdk9/cyclin T (IC50s = 1,290, 2,510, 1,710, 1,240, 4,640, and 50 nM, respectively). It halts the cell cycle at the G1 phase in Cdk4/6-dependent Hs68 cells (EC50 = 30 nM) but not Cdk4/6-independent A2058 cells. Trilaciclib (10-1,000 nM) prevents DNA damage and apoptosis induced by the DNA enzyme topoisomerase I inhibitor camptothecin (Cay-11694) in Hs68 cells used as a model of Cdk4/6-dependent hematopoietic stem and progenitor cells (HSPCs). It induces reversible cell cycle arrest of HSPCs in mice when administered at doses of 50, 100, or 150 mg/kg and prevents apoptosis of bone marrow cells induced by etoposide (Cay-12092) in mice at 100 mg/kg. Trilaciclib (150 mg/kg) also prevents myelosuppression induced by 5-fluorouracil (5-FU, Cay-14416) in mice. Formulations containing trilaciclib have been used in the treatment of late-stage small cell lung cancer to decrease the incidence of chemotherapy-induced myelosuppression.Formal Name: 7',8'-dihydro-2'-[[5-(4-methyl-1-piperazinyl)-2-pyridinyl]amino]-spiro[cyclohexane-1,9'(6'H)-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one, dihydrochloride. CAS Number: 1977495-97-8. Synonyms: G1T28. Molecular Formula: C24H30N8O . 2HCl. Formula Weight: 519.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Ethanol: Slightly soluble, PBS (pH 7.2): Slightly soluble. lambdamax: 216, 277, 366 nm. SMILES: O=C1NCC2(CCCCC2)N3C4=NC(NC5=CC=C(N6CCN(CC6)C)C=N5)=NC=C4C=C13.Cl.Cl. InChi Code: InChI=1S/C24H30N8O.2ClH/c1-30-9-11-31(12-10-30)18-5-6-20(25-15-18)28-23-26-14-17-13-19-22(33)27-16-24(7-3-2-4-8-24)32(19)21(17)29-23,,/h5-6,13-15H,2-4,7-12,16H2,1H3,(H,27,33)(H,25,26,28,29),2*1H. InChi Key: BRCYOXKEDFAUSA-UHFFFAOYSA-N.