ChemicalBook Product Catalog Biochemical Engineering Inhibitors MRTX-1719

MRTX-1719

Product NameMRTX-1719
CAS2630904-45-7
MFC23H18ClFN6O2
MW464.89
EINECS
MOL File2630904-45-7.mol

Chemical Properties

Density	1.58±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	Acetonitrile: Soluble DMSO: Soluble
pka	11.37±0.40(Predicted)
form	Solid
color	White to light yellow
InChIKey	BZKIOORWZAXIBA-UHFFFAOYSA-N
SMILES	CN1N=CC(C2=CC=C3C(NN=C(CN)C3=C2)=O)=C1C1C(=C(Cl)C=C(OC2CC2)C=1C#N)F

Usage And Synthesis

Uses

Navlimetostat is a potent, orally active, selective PRMT5MTA complex inhibitor, with IC50 of 3.6 and 20.5 nM for PRMT5MTA and PRMT5. Navlimetostat binds to the PRMT5MTA 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)	Cl_total (mL/min/kg)	V_dss (L/kg)	t_1/2 (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)	C_max (ug/mL)	AUC_inf (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

References

[1] Targeting the genetic and immunological drivers of cancer.
[2] CHRISTOPHER R. SMITH*. Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers[J]. Journal of Medicinal Chemistry, 2022, 65 3: 1749-1766. DOI: 10.1021/acs.jmedchem.1c01900

MRTX-1719 Supplier

MRTX-1719 manufacturers

Related Product Information

Send Inquriy