SOS1-IN-14

• CAT Number: I042745
• CAS Number: 2793405-20-4
• Molecular Formula: C29H29F3N6O2
• Molecular Weight: 550.57
• Purity: ≥95%
• Synonyms: 1-[(7S)-17-[[(1R)-1-[3-(difluoromethyl)-2-fluorophenyl]ethyl]amino]-15-methyl-10-oxa-2,5,14,16-tetrazatetracyclo[9.8.0.02,7.013,18]nonadeca-1(11),12,14,16,18-pentaene-5-carbonyl]cyclopropane-1-carbonitrile
• InChI: InChI=1S/C29H29F3N6O2/c1-16(19-4-3-5-20(25(19)30)26(31)32)34-27-21-12-23-24(13-22(21)35-17(2)36-27)40-11-6-18-14-37(9-10-38(18)23)28(39)29(15-33)7-8-29/h3-5,12-13,16,18,26H,6-11,14H2,1-2H3,(H,34,35,36)/t16-,18+/m1/s1
• InChIKey: UVNQICXVXBBWBT-AEFFLSMTSA-N
• SMILES: CC1=NC2=CC3=C(C=C2C(=N1)NC(C)C4=C(C(=CC=C4)C(F)F)F)N5CCN(CC5CCO3)C(=O)C6(CC6)C#N

SOS1-IN-14 is a potent, selective and orally active SOS1 inhibitor with an IC50 value of 3.9 nM. SOS1-IN-14 can be absorbed in the intestine via a P-glycoprotein-mediated efflux mechanism. SOS1-IN-14 can be used to research KRAS-mutated cancers. SOS1-IN-14 has better potent tumor suppression than BI-3406 (HY-125817)[1].
SOS1-IN-14 (compound 13c) exhibits cellular SOS1 inhibition with an IC50 of 21 nM[1].
SOS1-IN-14 has certain inhibition for CYP2D6, CYP2C9, CYP2C8 and CYP3A4 with IC50s of 2.5 μM, 6.5 μM, 43.3 μM and 54.3 μM, respectively, indicating that it has a certain risk of drug-drug interaction[1].
SOS1-IN-14 (50 mg/kg; p.o.; qd) exhibits 83.0% tumor suppression in Mia-paca-2 pancreas xenograft mice tumor models[1].
SOS1-IN-14 shows a favorable pharmacokinetic profile with a bioavailability of 86.8% in beagles[1].
Pharmacokinetic Parameters of SOS1-IN-14 (compound 13c) in ICR mice, Sprague-Dawley rats and Beagle dogs[1].

ICR Mice
Sprague–Dawley Rats
Beagle Dogs

Administration
p.o., 50 mg/kg
i.v., 2 mg/kg
p.o., 10 mg/kg
i.v., 2 mg/kg
p.o., 20 mg/kg

Tmax (h)
0.5
0.08
3
0.08
2

T1/2 (h)
4.61
1.17
2.32
3.83
6.68

Cmax (μg/mL)
2670
1261
265
568
1840

AUC0-24 (ng/mL·h)
32300
970
1683
2962
25725

CL (mL/min/kg)
/
2068
/
11.3
/

Vss (L/kg)
/
2126
/
3.88
/

F (%)
/
/
34.5
/
86.8

Kel (h-1)
0.265
/
/
/
/

MRT (h)
4.67
/
/
/
/

Reference

[1]. He H, et al. Discovery of Orally Bioavailable SOS1 Inhibitors for Suppressing KRAS-Driven Carcinoma. J Med Chem. 2022 Sep 29.
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