WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406533
CAS#: 1454846-35-5 (free base)
Description: Lorlatinib, also known as PF-06463922, is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity. Upon administration, ALK/ROS1 inhibitor PF-06463922 binds to and inhibits both ALK and ROS1 kinases. The kinase inhibition leads to disruption of ALK- and ROS1-mediated signaling and eventually inhibits tumor cell growth in ALK- and ROS1-overexpressing tumor cells. In addition, PF-06463922 is able to cross the blood brain barrier.
MedKoo Cat#: 406533
Name: Lorlatinib (PF-06463922)
CAS#: 1454846-35-5 (free base)
Chemical Formula: C21H19FN6O2
Exact Mass: 406.15535
Molecular Weight: 406.41
Elemental Analysis: C, 62.06; H, 4.71; F, 4.67; N, 20.68; O, 7.87
Related CAS #: 1924207-18-0 (acetate) 2135926-03-1 (maleate) 1454846-35-5 (free base) 2306217-6 (hydrate)
Synonym: PF06463922; PF 06463922; PF-06463922; PF-6463922; PF6463922; PF 6463922; Lorlatinib; Lorbrena.
IUPAC/Chemical Name: (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.
InChi Key: IIXWYSCJSQVBQM-LLVKDONJSA-N
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
SMILES Code: N#CC1=C(C(CN2C)=NN1C)C3=CN=C(N)C(O[C@H](C)C4=CC(F)=CC=C4C2=O)=C3
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.09.01
The following data is based on the product molecular weight 406.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Patel M, Chen J, McGrory S, O'Gorman M, Nepal S, Ginman K, Pithavala YK. The effect of itraconazole on the pharmacokinetics of lorlatinib: results of a phase I, open-label, crossover study in healthy participants. Invest New Drugs. 2019 Nov 14. doi: 10.1007/s10637-019-00872-7. [Epub ahead of print] Review. PubMed PMID: 31728714.
2: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548564/ PubMed PMID: 31643879.
3: Yang J, Gong W. Lorlatinib for the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer. Expert Rev Clin Pharmacol. 2019 Mar;12(3):173-178. doi: 10.1080/17512433.2019.1570846. Epub 2019 Jan 30. Review. PubMed PMID: 30657349.
4: Syed YY. Lorlatinib: First Global Approval. Drugs. 2019 Jan;79(1):93-98. doi: 10.1007/s40265-018-1041-0. Review. PubMed PMID: 30604291.
5: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK535599/ PubMed PMID: 30601608.
6: Akamine T, Toyokawa G, Tagawa T, Seto T. Spotlight on lorlatinib and its potential in the treatment of NSCLC: the evidence to date. Onco Targets Ther. 2018 Aug 22;11:5093-5101. doi: 10.2147/OTT.S165511. eCollection 2018. Review. PubMed PMID: 30174447; PubMed Central PMCID: PMC6110295.
7: Basit S, Ashraf Z, Lee K, Latif M. First macrocyclic 3(rd)-generation ALK inhibitor for treatment of ALK/ROS1 cancer: Clinical and designing strategy update of lorlatinib. Eur J Med Chem. 2017 Jul 7;134:348-356. doi: 10.1016/j.ejmech.2017.04.032. Epub 2017 Apr 13. Review. PubMed PMID: 28431340.
