An orally available inhibitor of ALK and ROS1
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PF-06463922

Item No. 18371

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
(10R)-7-amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-2H-4,8-methenopyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile
CAS Number
1454846-35-5
Synonyms
  • Lorlatinib
Molecular Formula
C21H19FN6O2
Formula Weight
406.4
Purity
≥98%
Formulation (Request formulation change)
A crystalline solid
Solubility(Learn about Variance in Solubility)
DMF: 5 mg/mLDMSO: 5 mg/mLEthanol: 1 mg/mLEthanol:PBS(pH 7.2) (1:1): 0.5 mg/mL
λmax
319 nm
SMILES
FC1=CC=C(C(N(C)CC2=NN(C)C(C#N)=C32)=O)C([C@@H](C)OC4=C(N)N=CC3=C4)=C1
InChi Code
InChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1
InChi Key
IIXWYSCJSQVBQM-LLVKDONJSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    Product Description

    PF-06463922 is an ATP-competitive, selective inhibitor of ALK (Ki = < 0.07 nM) and c-Ros oncogene 1 (ROS1, Ki = 0.7 nM).1 It has strong activity against all known ALK and ROS1 mutants identified in patients, including the EML4-L1196M mutant of ALK (Ki = < 0.02 nM).1,2,3 PF-06463922 is orally available, displaying inhibition of ALK phosphorylation and antitumor efficacy in a xenograft model expressing EML4-L1196M ALK.1,4 It demonstrates efficient blood-brain barrier penetration, produces brain tumor regression in mice harboring EML4-ALK tumors, and increases overall survival.2

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Johnson, T.W., Richardson, P.F., Bailey, S., et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J. Med. Chem. 57(11), 4720-4744 (2014).

    2. Awad, M.M., and Shaw, A.T. ALK inhibitors in non-small cell lung cancer: Crizotinib and beyond. Clin. Adv. Hematol. Oncol. 12(7), 429-439 (2014).

    3. Zou, H.Y., Li, Q., Engstrom, L.D., et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc. Natl. Acad. Sci. USA 112(11), 3493-3498 (2015).

    4. Yamazaki, S., Lam, J.L., Zou, H.Y., et al. Translational pharmacokinetic-pharmacodynamic modeling for an orally available novel inhibitor of anaplastic lymphoma kinase and c-Ros oncogene 1. J. Pharmacol. Exp. Ther. 351, 67-76 (2014).