MRTX0902

• CAT Number: I043968
• CAS Number: 2654743-22-1
• Molecular Formula: C22H24N6O
• Molecular Weight: 388.47
• Purity: ≥95%
• Synonyms: 2-methyl-3-[(1R)-1-[(4-methyl-7-morpholin-4-ylpyrido[3,4-d]pyridazin-1-yl)amino]ethyl]benzonitrile
• InChI: InChI=1S/C22H24N6O/c1-14-17(12-23)5-4-6-18(14)15(2)25-22-19-11-21(28-7-9-29-10-8-28)24-13-20(19)16(3)26-27-22/h4-6,11,13,15H,7-10H2,1-3H3,(H,25,27)/t15-/m1/s1
• InChIKey: ILPWEAHQRAWJIU-OAHLLOKOSA-N
• SMILES: CC1=C(C=CC=C1C(C)NC2=NN=C(C3=CN=C(C=C32)N4CCOCC4)C)C#N

MRTX0902 is an orally active and potent SOS1 inhibitor with an IC50 of 46 nM (WO2021127429A1; Example 12-10)[1].
MRTX0902 (compound 32) (1 μM; 0, 2, 4, 8, 15, and 30 minutes) shows a moderate Clint value of 195 mL/min/kg in human liver microsome and a low lipophilicity with cLogP of 3.4[1].
MRTX0902 displays high selectivity on SOS1 (Ki=2 nM) over SOS2 and EGFR (both Ki values >10,000 nM), MRTX0902 inhibits MKN1 cells with an IC50 value of 29 nM[1].
MRTX0902 (compound 32) (25, 50 mg/kg; p.o.; twice daily; 25 d) shows anti-tumor effect in mouse model and results tumor regression[1].
MRTX0902 (1-3 mg/kg for i.v. or 10-30 mg/kg for p.o.; single dose) exhibits good brain penetrance, low clearance, and high bioavailability[1].
PK Parameters for MRTX0902 across Species[1]

Parameter
Route
Dose (mg/kg)
Cl (mL/min/kg)
Vd,ss (L/kg)
T1/2(iv) (h)
F (%)

Mouse
IV/PO
3/30
4.4
0.28
1.3
69

Rat
IV/PO
1/10
14.6
0.28
0.62
83

Dog
IV/PO
2/10
7.6
0.48
0.86
38

Reference

[1]. Ketcham JM, et al. Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction. J Med Chem. 2022 Jul 28;65(14):9678-9690. 
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