MedKoo Cat#: 206498 | Name: Naporafenib HCl

Description:

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

Naporafenib, also known as LXH254, is an orally available inhibitor of all members of the serine/threonine protein kinase Raf family, with potential antineoplastic activity. Upon administration, pan-RAF inhibitor LXH254 binds to Raf proteins and inhibits Raf-mediated signal transduction pathways. This inhibits proliferation of Raf-overexpressing tumor cells. Raf protein kinases are critical enzymes in the Ras/Raf/MEK/ERK signaling pathway and are upregulated in a variety of cancer cell types..

Chemical Structure

Naporafenib HCl
Naporafenib HCl
CAS#LXH254 HCl

Theoretical Analysis

MedKoo Cat#: 206498

Name: Naporafenib HCl

CAS#: LXH254 HCl

Chemical Formula: C25H26ClF3N4O4

Exact Mass: 0.0000

Molecular Weight: 538.95

Elemental Analysis: C, 55.71; H, 4.86; Cl, 6.58; F, 10.58; N, 10.40; O, 11.87

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.
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Synonym
LXH254; LXH-254; LXH 254; LXH254 HCl; LXH254 hydrochloride; Naporafenib HCl; Naporafenib hydrochloride
IUPAC/Chemical Name
N-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide hydrochloride
InChi Key
SBMYWWMMWVWGKQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H25F3N4O4.ClH/c1-16-2-3-19(30-24(34)17-4-5-29-21(12-17)25(26,27)28)15-20(16)18-13-22(32-6-9-35-10-7-32)31-23(14-18)36-11-8-33;/h2-5,12-15,33H,6-11H2,1H3,(H,30,34);1H
SMILES Code
O=C(C1=CC(C(F)(F)F)=NC=C1)NC2=CC=C(C)C(C3=CC(OCCO)=NC(N4CCOCC4)=C3)=C2.[H]Cl
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, 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
2934.99.9001
More Info

Preparing Stock Solutions

The following data is based on the product molecular weight 538.95 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.

Recalculate based on batch purity %
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: Monaco KA, Delach S, Yuan J, Mishina Y, Fordjour P, Labrot E, McKay D, Guo R, Higgins S, Wang HQ, Liang J, Bui K, Green J, Aspesi P, Ambrose J, Mapa F, Griner L, Jaskelioff M, Fuller J, Crawford K, Pardee G, Widger S, Hammerman PS, Engelman JA, Stuart DD, Cooke VG, Caponigro G. LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors. Clin Cancer Res. 2021 Apr 1;27(7):2061-2073. doi: 10.1158/1078-0432.CCR-20-2563. Epub 2020 Dec 22. PMID: 33355204. 2: Janku F, Kim TM, Iyer G, Spreafico A, Elez E, de Jonge M, Yamamoto N, van der Wekken AJ, Ascierto PA, Maur M, Marmé F, Kiladjian JJ, Basu S, Baffert F, Buigues A, Chen C, Cooke V, Giorgetti E, Kim J, McCarthy F, Moschetta M, Dummer R. First-in-human study of naporafenib (LXH254) with or without spartalizumab in adult patients with advanced solid tumors harboring MAPK signaling pathway alterations. Eur J Cancer. 2024 Jan;196:113458. doi: 10.1016/j.ejca.2023.113458. Epub 2023 Nov 21. PMID: 38039779; PMCID: PMC11380116. 3: Li R, Ren M, Lu W, Yuan Y, Li J, Zhong W. A validated LC-MS/MS method for the determination of RAF inhibitor LXH254: Application to pharmacokinetic study in rat. Biomed Chromatogr. 2021 Feb;35(2):e4968. doi: 10.1002/bmc.4968. Epub 2020 Sep 16. PMID: 32881002. 4: de Braud F, Dooms C, Heist RS, Lebbe C, Wermke M, Gazzah A, Schadendorf D, Rutkowski P, Wolf J, Ascierto PA, Gil-Bazo I, Kato S, Wolodarski M, McKean M, Muñoz Couselo E, Sebastian M, Santoro A, Cooke V, Manganelli L, Wan K, Gaur A, Kim J, Caponigro G, Couillebault XM, Evans H, Campbell CD, Basu S, Moschetta M, Daud A. Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study. J Clin Oncol. 2023 May 10;41(14):2651-2660. doi: 10.1200/JCO.22.02018. Epub 2023 Mar 22. PMID: 36947734. 5: Tkacik E, Li K, Gonzalez-Del Pino G, Ha BH, Vinals J, Park E, Beyett TS, Eck MJ. Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib. J Biol Chem. 2023 May;299(5):104634. doi: 10.1016/j.jbc.2023.104634. Epub 2023 Mar 22. PMID: 36963492; PMCID: PMC10149214. 6: Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist RS, Sun JM, Min Kim T, Reguart N, Sanmamed MF, Felip E, Garrido P, Santoro A, Bootle D, Couillebault XM, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer. 2024 Nov;197:107964. doi: 10.1016/j.lungcan.2024.107964. Epub 2024 Sep 26. PMID: 39383771. 7: Christen D, Lauinger M, Brunner M, Dengjel J, Brummer T. The mTOR pathway controls phosphorylation of BRAF at T401. Cell Commun Signal. 2024 Sep 2;22(1):428. doi: 10.1186/s12964-024-01808-2. PMID: 39223665; PMCID: PMC11370054. 8: Park S, Kim TM, Cho SY, Kim S, Oh Y, Kim M, Keam B, Kim DW, Heo DS. Combined blockade of polo-like kinase and pan-RAF is effective against NRAS-mutant non- small cell lung cancer cells. Cancer Lett. 2020 Dec 28;495:135-144. doi: 10.1016/j.canlet.2020.09.018. Epub 2020 Sep 23. PMID: 32979462. 9: Vasta JD, Michaud A, Zimprich CA, Beck MT, Swiatnicki MR, Zegzouti H, Thomas MR, Wilkinson J, Crapster JA, Robers MB. Protomer selectivity of type II RAF inhibitors within the RAS/RAF complex. Cell Chem Biol. 2023 Nov 16;30(11):1354-1365.e6. doi: 10.1016/j.chembiol.2023.07.019. Epub 2023 Aug 28. PMID: 37643616. 10: Lauinger M, Christen D, Klar RFU, Roubaty C, Heilig CE, Stumpe M, Knox JJ, Radulovich N, Tamblyn L, Xie IY, Horak P, Forschner A, Bitzer M, Wittel UA, Boerries M, Ball CR, Heining C, Glimm H, Fröhlich M, Hübschmann D, Gallinger S, Fritsch R, Fröhling S, O'Kane GM, Dengjel J, Brummer T. BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability. Sci Adv. 2023 Sep;9(35):eade7486. doi: 10.1126/sciadv.ade7486. Epub 2023 Sep 1. PMID: 37656784; PMCID: PMC11804575.