Labuxtinib  (Synonyms: EVT-8565072; THB335)

Labuxtinib (EVT-8565072; THB335) is a potent dual inhibitor of c-Kit and PDGFR. Labuxtinib exhibits potent inhibitory activity against wild-type c-Kit (IC₅₀ = 0.005 μM). Labuxtinib inhibits SCF-dependent and PDGF-dependent cell proliferation, and blocks the proliferation of cells dependent on c-Kit or PDGFR signaling pathways. In animal models of skin allergy, Labuxtinib depletes skin mast cells and significantly alleviates anaphylactic shock responses. Labuxtinib can be used in research on mast cell-related diseases, respiratory diseases, inflammatory diseases, fibrotic diseases, metabolic diseases, and other related conditions^[1][2].

Labuxtinib (F13) inhibits SCF-dependent proliferation in human Mo7e cells and PDGF-dependent proliferation in rat A10 cells and human TG/HA-VSMC cells^[1].
Labuxtinib blocks the proliferation of cells dependent on c-Kit or PDGFR signaling pathways and shows potent c-Kit inhibitory activity with an IC₅₀ value of 7 nM^[1].
Labuxtinib (THB33) acts as a competitive inhibitor at the KIT ATP-binding pocket to block KIT signaling^[3][4].
Labuxtinib inhibits wild-type KIT phosphorylation and KIT-dependent cellular activity, with IC₅₀ values of 0.005 μM and 0.0079 μM respectively^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Labuxtinib (p.o.) yields favorable oral exposure parameters in beagle dogs, with improved bioavailability relative to unformulated active^[2].
Labuxtinib induces dose-dependent depletion of dermal mast cells and reduces cutaneous anaphylaxis in a rat passive cutaneous anaphylaxis model^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

377.37

C₂₀H₁₆FN₅O₂

1426449-01-5

Solid

White to light yellow

CC1=CC=C(C2=NOC([C@@H]3[C@H](C3)F)=N2)C=C1NC(C4=CN=C5N4C=CC=C5)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Vince Yeh, et al. COMPOUNDS AND COMPOSITIONS AS c-KIT KINASE INHIBITORS, WO, WO2013033070A1, 2013-03-07.

  [2]. Gregg F. Keaney, et al. Pharmaceutical compositions of a selective c-kit kinase inhibitor and methods for making and using same, WO, WO2022109595A1, 2022-05-27.

  [3]. Bachtell N, et al. First-in-human study of THB335, an oral small molecule inhibitor of Wild Type KIT Receptor Tyrosine Kinase: Initial Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) Results from Single Ascending Dose Cohorts. J Allergy Clin Immunol. 2025;155(2 Suppl 1):AB220.

  [4]. Turner M, et al. THB335 is a potent and selective oral small molecule inhibitor of wild type KIT. J Allergy Clin Immunol. 2025;155(2 Suppl 1):AB98.

  [5]. Turner M, et al. THB335 is a potent and selective oral small molecule inhibitor of wild type KIT. J Allergy Clin Immunol. 2025;155(2 Suppl 1):AB98.