| Identification | Back Directory | [Name]
MRTX-1719 | [CAS]
2630904-45-7 | [Synonyms]
Benzonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-4-chloro-6-(cyclopropyloxy)-3-fluoro-, (2R)- | [Molecular Formula]
C23H18ClFN6O2 | [MOL File]
2630904-45-7.mol | [Molecular Weight]
464.89 |
| Chemical Properties | Back Directory | [density ]
1.58±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
11.37±0.40(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
Navlimetostat is a potent, orally active, selective PRMT5?MTA complex inhibitor, with IC50 of 3.6 and 20.5 nM for PRMT5?MTA and PRMT5. Navlimetostat binds to the PRMT5?MTA complex, with KD value of 0.14 pM. Navlimetostat shows antineoplastic activity in vitro and in vivo, and can be used for cancer study[1][2]. | [Biological Activity]
MRTX-1719 is a potent first-in-class selective inhibitor of the PRMT5/MTA complex, with an IC50 of less than 10 nM in PRMT5/MTA MTAPDEL SDMA cells[1]. | [in vivo]
Navlimetostat (12.5-100 mg/kg/d for p.o., 21 day) reduces the tumor growth in Lu-99 orthotopic xenograft tumor models[2].
Pharmacokinetic Analysis [2]
| Model | Route | Dose (mg/kg) | Cltotal (mL/min/kg) | Vdss (L/kg) | t1/2 (h) | | CD-1 mouse. | i.v. | 3 | 83 | 6.3 | 1.5 | | Beagle dog | i.v. | 2 | 14 | 3.4 | 4.8 | | Cynomolgus monkey | i.v. | 2 | 15 | 2.3 | 6.1 |
| Model | Route | Dose (mg/kg) | Cmax (ug/mL) | AUCinf (h*ug/mL) | F (%) | | CD-1 mouse. | p.o. | 30 | 1.16 | 4.85 | 80 | | Beagle dog | p.o. | 10 | 1.40 | 7.47 | 59 | | Cynomolgus monkey | p.o. | 10 | / | / | 41 |
| Animal Model: | Lu-99 (an MTAP/CDKN2A-deleted human lung cancer cell line ) xenograft tumor models[2] | | Dosage: | 12.5, 25, 50, and 100 mg/kg/d, 21 day | | Administration: | Oral gavage | | Result: | Reduced the tumor volume with 86% tumor growth inhibition (TGI) at 50 mg/kg and 88% TGI at 100 mg/kg. |
| [IC 50]
PRMT5 | [storage]
Store at -20°C | [References]
[1]. Targeting the genetic and immunological drivers of cancer. |
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