Lorlatinib (PF-06463922)
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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.


Price and Availability

Size
Price

25mg
USD 150
200mg
USD 750
2g
USD 4250
Size
Price

50mg
USD 250
500mg
USD 1450
5g
USD 5650
Size
Price

100mg
USD 450
1g
USD 2450
10g
USD 8950

Lorlatinib (PF-06463922), purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 1 g may be 2 weeks.


Chemical Structure

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Theoretical Analysis

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

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


Technical Data

Appearance:
White to off-white solid powder

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

Certificate of Analysis:

Safety Data Sheet (MSDS):

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).

Harmonized System Code:
2934.99.09.01


Additional Information

  
 
 
 


References

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2: Duruisseaux M. Lorlatinib: a new treatment option for ROS1-positive lung cancer. Lancet Oncol. 2019 Oct 25. pii: S1470-2045(19)30716-8. doi: 10.1016/S1470-2045(19)30716-8. [Epub ahead of print] PubMed PMID: 31669156.

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11: Pailler E, Faugeroux V, Oulhen M, Mezquita L, Laporte M, Honoré A, Lecluse Y, Queffelec P, NgoCamus M, Nicotra C, Remon J, Lacroix L, Planchard D, Friboulet L, Besse B, Farace F. Acquired Resistance Mutations to ALK Inhibitors Identified by Single Circulating Tumor Cell Sequencing in ALK-Rearranged Non-Small-Cell Lung Cancer. Clin Cancer Res. 2019 Aug 22. doi: 10.1158/1078-0432.CCR-19-1176. [Epub ahead of print] PubMed PMID: 31439588.

12: McCusker MG, Russo A, Scilla KA, Mehra R, Rolfo C. How I treat ALK-positive non-small cell lung cancer. ESMO Open. 2019 Jul 20;4(Suppl 2):e000524. doi: 10.1136/esmoopen-2019-000524. eCollection 2019. Review. PubMed PMID: 31423342; PubMed Central PMCID: PMC6677959.

13: Kong X, Pan P, Sun H, Xia H, Wang X, Li Y, Hou T. Drug Discovery Targeting Anaplastic Lymphoma Kinase (ALK). J Med Chem. 2019 Aug 26. doi: 10.1021/acs.jmedchem.9b00446. [Epub ahead of print] PubMed PMID: 31419130.

14: Katayama R, Gong B, Togashi N, Miyamoto M, Kiga M, Iwasaki S, Kamai Y, Tominaga Y, Takeda Y, Kagoshima Y, Shimizu Y, Seto Y, Oh-Hara T, Koike S, Nakao N, Hanzawa H, Watanabe K, Yoda S, Yanagitani N, Hata AN, Shaw AT, Nishio M, Fujita N, Isoyama T. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun. 2019 Aug 9;10(1):3604. doi: 10.1038/s41467-019-11496-z. PubMed PMID: 31399568; PubMed Central PMCID: PMC6688997.

15: Makimoto G, Ohashi K, Tomida S, Nishii K, Matsubara T, Kayatani H, Higo H, Ninomiya K, Sato A, Watanabe H, Kano H, Ninomiya T, Kubo T, Rai K, Ichihara E, Hotta K, Tabata M, Toyooka S, Takata M, Maeda Y, Kiura K. Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden. J Thorac Oncol. 2019 Nov;14(11):2009-2018. doi: 10.1016/j.jtho.2019.07.017. Epub 2019 Jul 30. PubMed PMID: 31374369.

16: Dagogo-Jack I, Rooney M, Lin JJ, Nagy RJ, Yeap BY, Hubbeling H, Chin E, Ackil J, Farago AF, Hata AN, Lennerz JK, Gainor JF, Lanman RB, Shaw AT. Treatment with Next-Generation ALK Inhibitors Fuels Plasma ALK Mutation Diversity. Clin Cancer Res. 2019 Jul 29. doi: 10.1158/1078-0432.CCR-19-1436. [Epub ahead of print] PubMed PMID: 31358542.

17: Karachaliou N, Fernandez Bruno M, Bracht JWP, Rosell R. Profile of alectinib for the treatment of ALK-positive non-small cell lung cancer (NSCLC): patient selection and perspectives. Onco Targets Ther. 2019 Jun 13;12:4567-4575. doi: 10.2147/OTT.S174548. eCollection 2019. Review. PubMed PMID: 31354290; PubMed Central PMCID: PMC6580130.

18: Gafer H, de Waard Q, Compter A, van den Heuvel M. Rapid regression of neurological symptoms in patients with metastasised ALK+ lung cancer who are treated with lorlatinib: a report of two cases. BMJ Case Rep. 2019 Jul 24;12(7). pii: e227299. doi: 10.1136/bcr-2018-227299. PubMed PMID: 31345828; PubMed Central PMCID: PMC6663151.

19: Wrona A. Management of CNS disease in ALK-positive non-small cell lung cancer: Is whole brain radiotherapy still needed? Cancer Radiother. 2019 Sep;23(5):432-438. doi: 10.1016/j.canrad.2019.03.009. Epub 2019 Jul 19. Review. PubMed PMID: 31331844.

20: Hamilton G, Hochmair MJ. An evaluation of brigatinib as a promising treatment option for non-small cell lung cancer. Expert Opin Pharmacother. 2019 Sep;20(13):1551-1561. doi: 10.1080/14656566.2019.1643839. Epub 2019 Jul 22. PubMed PMID: 31328968.