MRTX9768 hydrochloride 是一种有效的、选择性的、具有口服活性的、首创的 PRMT5-MTA 复合体抑制剂。

MRTX9768 hydrochloride is a potent, selective, orally active, first-in-class PRMT5-MTA complex inhibitor.

Solid

PRMT5?MTA

MRTX9768 inhibits SDMA and cell proliferation in HCT116 MTAP-del cells (SDMA IC50 3 nM; prolif. IC50 11 nM) with marked selectivity over HCT116 MTAP-WT cells (SDMA IC50 544 nM; prolif. IC50 861 nM).
MRTX9768 (0-250 nM) results in LU99 SDMA inhibition maintaining after 3-hr drug treatment followed by 4-day washout (exhibiting tight binding and prolonged PRMT5?MTA occupancy).
has not independently confirmed the accuracy of these methods. They are for reference only.

In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow.
MRTX9768 selectively targets MTAP/CDKN2A-deleted tumors (such as glioblastoma).
MRTX9768 (PO dose 30 mg/kg in CD-1 mouse and beagle dog, 10 mg/kg in cynomolgus monkey) has a favorable ADME profile (>50% bioavailability in mice and dogs, moderate to high clearance, No changes in RBC parameters when administered well above efficacious concentrations (1000 mg/kg)).
MRTX9768 (100 mg/kg, orally, BID, 6/21 days) results in SDMA inhibition maintaining 3 days after dosing is stopped.
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture and light In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

[1]. Christopher R. Smith, et al. Abstract LB003: Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors. AACR Annual Meeting 2021; April 10-15, 2021 and
[2]. Yingqing Chen, et al. Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms. Biomed Pharmacother. 2021 Oct 4;144:112252.

In Vitro: H₂O : 40 mg/mL (86.79 mM; Need ultrasonic)DMSO : 19 mg/mL (41.22 mM; Need ultrasonic)配制储备液