Selpercatinib | LOXO-292 | CAS#2152628-33-4 | RET inhibitor

MedKoo Cat#: 584819 | Name: Selpercatinib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Selpercatinib, also known as LOXO-292, is a potent and selective RET inhibitor with antineoplastic properties. LOXO-292 selectively binds to and targets various RET mutants and RET-containing fusion products. This results in an inhibition of cell growth of tumors cells that exhibit increased RET activity. Selpercatinib was approved in May 2020.

Chemical Structure

Selpercatinib

CAS#2152628-33-4 (free base)

Theoretical Analysis

MedKoo Cat#: 584819

Name: Selpercatinib

CAS#: 2152628-33-4 (free base)

Chemical Formula: C29H31N7O3

Exact Mass: 525.2488

Molecular Weight: 525.61

Elemental Analysis: C, 66.27; H, 5.95; N, 18.65; O, 9.13

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 225.00	Ready to ship
50mg	USD 385.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,050.00	Ready to ship
500mg	USD 2,250.00	Ready to ship
1g	USD 3,650.00	Ready to ship
2g	USD 6,250.00	Ready to ship

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Related CAS #

2152628-33-4 (free base) 2306313-13-1 (HCl) 2306313-14-2 (sulfate) 2306313-16-4 (tosylate) 2306313-17-5 (mesylate) 2306313-19-7 (besylate) 2306313-23-3 (maleate) 2306313-28-8 (fumarate) 2306313-27-7 (tartrate) 2306313-29-9 (citrate)

Synonym

LOXO-292; LOXO292; LOXO 292; ARRY-192; ARRY192; ARRY 192; Selpercatinib;

IUPAC/Chemical Name

6-(2-hydroxy-2-methylpropoxy)-4-(6-{6-[(6-methoxypyridin-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-3-yl}pyridin-3- yl)pyrazolo[1,5-a]pyridine-3-carbonitrile

InChi Key

XIIOFHFUYBLOLW-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H31N7O3/c1-29(2,37)18-39-24-9-25(28-21(10-30)13-33-36(28)17-24)20-5-6-26(31-12-20)34-15-22-8-23(16-34)35(22)14-19-4-7-27(38-3)32-11-19/h4-7,9,11-13,17,22-23,37H,8,14-16,18H2,1-3H3

SMILES Code

N#CC1=C2C(C3=CC=C(N4CC(C5)N(CC6=CC=C(OC)N=C6)C5C4)N=C3)=CC(OCC(C)(O)C)=CN2N=C1

Appearance

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

Shelf Life

>3 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

2934.99.9001

More Info

RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and progression of these cancers.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C21R05B03

QC Data

View QC data: current batch, Lot#C21R05B03

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Selpercatinib is a potent, selective RET kinase inhibitor with IC50 values of 14.0 nM, 24.1 nM, and 530.7 nM for RET (WT), RET (V804M), and RET (G810R), respectively.

In vitro activity:

In this study, the in vitro activity of selpercatinib, a tyrosine kinase inhibitor, was investigated in a patient with medullary thyroid cancer harboring the RET Δ898-901 mutation. Selpercatinib effectively inhibited the growth of cells carrying RET Δ898-901, demonstrating an IC50 of approximately 3 nM. Reference: JCO Precis Oncol. 2023 Aug;7:e2300052. https://pubmed.ncbi.nlm.nih.gov/37535881/

In vivo activity:

Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive non-small-cell lung cancer (NSCLC). Median progression-free survival was 24.8 months with selpercatinib and 11.2 months with control treatmen. The percentage of patients with an objective response was 84% with selpercatinib and 65% with control treatment. Reference: N Engl J Med. 2023 Nov 16;389(20):1839-1850. https://pubmed.ncbi.nlm.nih.gov/37870973/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	20.0	38.05

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 525.61 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

Formulation protocol:

1. Porcelli T, Moccia M, De Stefano MA, Ambrosio R, Capoluongo E, Santoro M, Hadoux J, Schlumberger M, Carlomagno F, Salvatore D. D898_E901 RET Deletion Is Oncogenic, Responds to Selpercatinib, and Treatment Resistance Can Arise Via RET-Independent Mechanisms. JCO Precis Oncol. 2023 Aug;7:e2300052. doi: 10.1200/PO.23.00052. PMID: 37535881; PMCID: PMC10581602. 2. Zhou C, Solomon B, Loong HH, Park K, Pérol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. doi: 10.1056/NEJMoa2309457. Epub 2023 Oct 21. PMID: 37870973. 3. Le D, Konda B. Selpercatinib for adult patients with locally advanced or metastatic RET-altered solid tumors. Expert Rev Anticancer Ther. 2023 Jul-Dec;23(11):1117-1122. doi: 10.1080/14737140.2023.2267754. Epub 2023 Oct 27. PMID: 37795873.

In vitro protocol:

In vivo protocol:

1. Zhou C, Solomon B, Loong HH, Park K, Pérol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. doi: 10.1056/NEJMoa2309457. Epub 2023 Oct 21. PMID: 37870973. 2. Le D, Konda B. Selpercatinib for adult patients with locally advanced or metastatic RET-altered solid tumors. Expert Rev Anticancer Ther. 2023 Jul-Dec;23(11):1117-1122. doi: 10.1080/14737140.2023.2267754. Epub 2023 Oct 27. PMID: 37795873.

1: Russo A, Lopes AR, McCusker MG, Garrigues SG, Ricciardi GR, Arensmeyer KE, Scilla KA, Mehra R, Rolfo C. New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1). Curr Oncol Rep. 2020 Apr 16;22(5):48. doi: 10.1007/s11912-020-00909-8. PMID: 32296961. 2: Dias-Santagata D, Lennerz JK, Sadow PM, Frazier RP, Govinda Raju S, Henry D, Chung T, Kherani J, Rothenberg SM, Wirth LJ. Response to RET-Specific Therapy in RET Fusion-Positive Anaplastic Thyroid Carcinoma. Thyroid. 2020 Apr 15. doi: 10.1089/thy.2019.0477. Epub ahead of print. PMID: 32292131. 3: Zhao Z, Fu T, Gao J, Xu Y, Wu X, Chen W, Li X, Yu R, Shao YW, Li M, Yao Y. Identifying novel oncogenic RET mutations and characterising their sensitivity to RET-specific inhibitors. J Med Genet. 2020 Apr 13:jmedgenet-2019-106546. doi: 10.1136/jmedgenet-2019-106546. Epub ahead of print. PMID: 32284345. 4: Solomon BJ, Tan L, Lin JJ, Wong SQ, Hollizeck S, Ebata K, Tuch BB, Yoda S, Gainor JF, Sequist LV, Oxnard GR, Gautschi O, Drilon A, Subbiah V, Khoo C, Zhu EY, Nguyen M, Henry D, Condroski KR, Kolakowski GR, Gomez E, Ballard J, Metcalf AT, Blake JF, Dawson SJ, Blosser W, Stancato LF, Brandhuber BJ, Andrews S, Robinson BG, Rothenberg SM. RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies. J Thorac Oncol. 2020 Apr;15(4):541-549. doi: 10.1016/j.jtho.2020.01.006. Epub 2020 Jan 24. PMID: 31988000. 5: Tiedje V, Fagin JA. Therapeutic breakthroughs for metastatic thyroid cancer. Nat Rev Endocrinol. 2020 Feb;16(2):77-78. doi: 10.1038/s41574-019-0307-2. PMID: 31819229. 6: Durham BH, Lopez Rodrigo E, Picarsic J, Abramson D, Rotemberg V, De Munck S, Pannecoucke E, Lu SX, Pastore A, Yoshimi A, Mandelker D, Ceyhan-Birsoy O, Ulaner GA, Walsh M, Yabe M, Petrova-Drus K, Arcila ME, Ladanyi M, Solit DB, Berger MF, Hyman DM, Lacouture ME, Erickson C, Saganty R, Ki M, Dunkel IJ, Santa-María López V, Mora J, Haroche J, Emile JF, Decaux O, Geissmann F, Savvides SN, Drilon A, Diamond EL, Abdel-Wahab O. Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms. Nat Med. 2019 Dec;25(12):1839-1842. doi: 10.1038/s41591-019-0653-6. Epub 2019 Nov 25. PMID: 31768065; PMCID: PMC6898787. 7: Li AY, McCusker MG, Russo A, Scilla KA, Gittens A, Arensmeyer K, Mehra R, Adamo V, Rolfo C. RET fusions in solid tumors. Cancer Treat Rev. 2019 Dec;81:101911. doi: 10.1016/j.ctrv.2019.101911. Epub 2019 Oct 30. PMID: 31715421. 8: Hillier K, Hughes A, Shamberger RC, Shusterman S, Perez-Atayde AR, Wassner AJ, Iafrate AJ, Dubuc A, Janeway KA, Rothenberg SM, Cox MC, Randolph GW, Wirth LJ, Tsai H, Church A, DuBois SG. A Novel ALK Fusion in Pediatric Medullary Thyroid Carcinoma. Thyroid. 2019 Nov;29(11):1704-1707. doi: 10.1089/thy.2019.0041. PMID: 31650892. 9: Ackermann CJ, Stock G, Tay R, Dawod M, Gomes F, Califano R. Targeted Therapy For RET-Rearranged Non-Small Cell Lung Cancer: Clinical Development And Future Directions. Onco Targets Ther. 2019 Sep 24;12:7857-7864. doi: 10.2147/OTT.S171665. PMID: 31576143; PMCID: PMC6767757. 10: Guo R, Schreyer M, Chang JC, Rothenberg SM, Henry D, Cotzia P, Kris MG, Rekhtman N, Young RJ, Hyman DM, Drilon A. Response to Selective RET Inhibition With LOXO-292 in a Patient With RET Fusion-Positive Lung Cancer With Leptomeningeal Metastases. JCO Precis Oncol. 2019;3:10.1200/PO.19.00021. doi: 10.1200/PO.19.00021. Epub 2019 Jun 3. PMID: 31485557; PMCID: PMC6724540. 11: O'Leary C, Xu W, Pavlakis N, Richard D, O'Byrne K. Rearranged During Transfection Fusions in Non-Small Cell Lung Cancer. Cancers (Basel). 2019 May 3;11(5):620. doi: 10.3390/cancers11050620. PMID: 31058838; PMCID: PMC6562639. 12: Bronte G, Ulivi P, Verlicchi A, Cravero P, Delmonte A, Crinò L. Targeting RET-rearranged non-small-cell lung cancer: future prospects. Lung Cancer (Auckl). 2019 Mar 20;10:27-36. doi: 10.2147/LCTT.S192830. PMID: 30962732; PMCID: PMC6433115. 13: Subbiah V, Velcheti V, Tuch BB, Ebata K, Busaidy NL, Cabanillas ME, Wirth LJ, Stock S, Smith S, Lauriault V, Corsi-Travali S, Henry D, Burkard M, Hamor R, Bouhana K, Winski S, Wallace RD, Hartley D, Rhodes S, Reddy M, Brandhuber BJ, Andrews S, Rothenberg SM, Drilon A. Selective RET kinase inhibition for patients with RET-altered cancers. Ann Oncol. 2018 Aug 1;29(8):1869-1876. doi: 10.1093/annonc/mdy137. PMID: 29912274; PMCID: PMC6096733. 14: LOXO-292 Reins In RET-Driven Tumors. Cancer Discov. 2018 Aug;8(8):904-905. doi: 10.1158/2159-8290.CD-NB2018-070. Epub 2018 Jun 2. PMID: 29860229. 15: Sabari JK, Siau ED, Drilon A. Targeting RET-rearranged lung cancers with multikinase inhibitors. Oncoscience. 2017 Apr 14;4(3-4):23-24. doi: 10.18632/oncoscience.345. PMID: 28540330; PMCID: PMC5441470.