LPM4870108 is a potent and orally active pan-Trk (WT and MT) inhibitor, with IC50s of 0.2 nM, 2.4 nM, 3.5 nM and 2.3 nM for TrkC, TrkA, TrkAG595R and TrkAG667C, respectively. LPM4870108 shows selectivity for Trk over ALK (IC50=182 nM). LPM4870108 exhibits anti-tumor activity.

Product information

Molecular Weight: 410.40

Formula: C20H19FN6O3

Chemical Name: (R, 3'E, 4'E)-5'-fluorospiro[cyclopropane-1, 6'-5-oxa-7-aza-2(4, 3)-morpholina-1(5, 3)-pyrazolo[1, 5-a]pyrimidina-3(3, 2)-pyridinacyclooctaphan]-8'-one

Smiles: O=C1NC2(CC2)OCC2=NC=C(F)C=C2[C@@H]2COCCN2C2C=CN3N=CC1=C3N=2

InChiKey: QWIHVVXROOETII-INIZCTEOSA-N

InChi: InChI=1S/C20H19FN6O3/c21-12-7-13-15(22-8-12)10-30-20(2-3-20)25-19(28)14-9-23-27-4-1-17(24-18(14)27)26-5-6-29-11-16(13)26/h1,4,7-9,16H,2-3,5-6,10-11H2,(H,25,28)/t16-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

LPM4870108 (compound 10) inhibits the activities of TrkA, TrkB, and TRC with high selectivity at 0.5 μM (kinase activity remaining, <10%) and slightly inhibit the activities of ALK and ROS1 (kinase activity remaining, 10-30%).

In Vivo:

LPM4870108 (compound 10) (5-20 mg/kg; p.o. once daily for 21 days) inhibits tumor growth in BaF3-NTRK xenograft tumor models. LPM4870108 (2 mg/kg; a single i.v.) exhibits terminal half-life (t1/2) (male 0.87 h, 2.21 h), the Cl (male 19.3 mL/kg/min, female 8.19 mL/kg/min), and the AUC0-t (male 4191 nM•h, female 10282 nM•h) in rats. LPM4870108 (10 mg/kg; a single p.o.) exhibits oral bioavailability (male 56.0%, female 61.9%), Cmax (male 6384 nM, female 6628 nM) and Tmax (male 0.667 h, female 0.667 h) in rats.

Products are for research use only. Not for human use.