RXDX-105 (CEP-32496)
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MedKoo CAT#: 205903

CAS#: 1188910-76-0 (free base)

Description: RXDX-105, also known as Agerafenib, CEP-32496 and AC013773, is an orally available v-raf murine sarcoma viral oncogene homolog B1 (B-raf) serine/threonine protein kinase inhibitor with potential antineoplastic activity.


Chemical Structure

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RXDX-105 (CEP-32496)
CAS# 1188910-76-0 (free base)

Theoretical Analysis

MedKoo Cat#: 205903
Name: RXDX-105 (CEP-32496)
CAS#: 1188910-76-0 (free base)
Chemical Formula: C24H22F3N5O5
Exact Mass: 517.16
Molecular Weight: 517.470
Elemental Analysis: C, 55.71; H, 4.29; F, 11.01; N, 13.53; O, 15.46

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2450 Ready to ship
1g USD 3450 2 Weeks
Bulk inquiry

Synonym: RXDX-105; RXDX 105; RXDX105; CEP32496; CEP-32496; CEP 32496; AC013773; AC 013773; AC-013773. Agerafenib

IUPAC/Chemical Name: 1-(3-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea

InChi Key: DKNUPRMJNUQNHR-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H22F3N5O5/c1-23(2,24(25,26)27)19-11-20(32-37-19)31-22(33)30-13-6-5-7-14(8-13)36-21-15-9-17(34-3)18(35-4)10-16(15)28-12-29-21/h5-12H,1-4H3,(H2,30,31,32,33)

SMILES Code: O=C(NC1=NOC(C(C)(C)C(F)(F)F)=C1)NC2=CC=CC(OC3=C4C=C(OC)C(OC)=CC4=NC=N3)=C2

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: 2934.99.9001

More Info: Related CAS# CAS#1188910-76-0 (free base) CAS#1227678-26-3 ( HCl salt).    

Biological target: RXDX-105 specifically and selectively inhibits the activity of the mutated form (V600E) of B-raf kinase with a Kd of 14 nM. This inhibits the activation of the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway and may result in a decrease in the proliferation of tumor cells expressing the mutated B-raf gene.
In vitro activity: Treatment with RXDX-105 resulted in a substantial reduction in neuroblastoma cell viability and proliferation. It effectively inhibited key molecular signaling pathways, including the phosphorylation of RET, MEK, and ERK kinases, suggesting its potential to disrupt critical cellular processes. RXDX-105 induced both apoptosis and cell cycle arrest in neuroblastoma cells. Reference: Oncotarget. 2019 Oct 29; 10(59): 6323–6333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824878/
In vivo activity: Carbon-11-labeled RXDX-105 ([11C]RXDX-105) demonstrated high binding affinity for BRAFV600E-positive A375 melanoma cells and densely accumulated in tumor tissue sections in mice with the BRAFV600E mutation. There was a slow but continuous accumulation of [11C]RXDX-105 in melanoma tumors. [11C]RXDX-105 has high stability in plasma. These findings suggest that [11C]RXDX-105 could be a potential candidate for noninvasive personalized diagnostic applications. Reference: Mol Imaging. 2018 Jan-Dec;17:1536012118795952. https://pubmed.ncbi.nlm.nih.gov/30251592/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 38.65
DMF 10.0 19.32
Ethanol 2.0 3.86

Preparing Stock Solutions

The following data is based on the product molecular weight 517.47 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
Formulation protocol: 1. Flynn SM, Lesperance J, Macias A, Phanhthilath N, Paul MR, Kim JW, Tamayo P, Zage PE. The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo. Oncotarget. 2019 Oct 29;10(59):6323-6333. doi: 10.18632/oncotarget.27259. PMID: 31695841; PMCID: PMC6824878. 2. James J, Ruggeri B, Armstrong RC, Rowbottom MW, Jones-Bolin S, Gunawardane RN, Dobrzanski P, Gardner MF, Zhao H, Cramer MD, Hunter K, Nepomuceno RR, Cheng M, Gitnick D, Yazdanian M, Insko DE, Ator MA, Apuy JL, Faraoni R, Dorsey BD, Williams M, Bhagwat SS, Holladay MW. CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity. Mol Cancer Ther. 2012 Apr;11(4):930-41. doi: 10.1158/1535-7163.MCT-11-0645. Epub 2012 Feb 7. PMID: 22319199. 3. Jiang C, Xie L, Zhang Y, Fujinaga M, Mori W, Kurihara Y, Yamasaki T, Wang F, Zhang MR. Pharmacokinetic Evaluation of [11C]CEP-32496 in Nude Mice Bearing BRAFV600E Mutation-Induced Melanomas. Mol Imaging. 2018 Jan-Dec;17:1536012118795952. doi: 10.1177/1536012118795952. PMID: 30251592; PMCID: PMC6156206. 4. Shimoda Y, Yui J, Fujinaga M, Xie L, Kumata K, Ogawa M, Yamasaki T, Hatori A, Kawamura K, Zhang MR. [(11)C-carbonyl]CEP-32496: radiosynthesis, biodistribution and PET study of brain uptake in P-gp/BCRP knockout mice. Bioorg Med Chem Lett. 2014 Aug 1;24(15):3574-7. doi: 10.1016/j.bmcl.2014.05.045. Epub 2014 Jun 2. PMID: 24930831.
In vitro protocol: 1. Flynn SM, Lesperance J, Macias A, Phanhthilath N, Paul MR, Kim JW, Tamayo P, Zage PE. The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo. Oncotarget. 2019 Oct 29;10(59):6323-6333. doi: 10.18632/oncotarget.27259. PMID: 31695841; PMCID: PMC6824878. 2. James J, Ruggeri B, Armstrong RC, Rowbottom MW, Jones-Bolin S, Gunawardane RN, Dobrzanski P, Gardner MF, Zhao H, Cramer MD, Hunter K, Nepomuceno RR, Cheng M, Gitnick D, Yazdanian M, Insko DE, Ator MA, Apuy JL, Faraoni R, Dorsey BD, Williams M, Bhagwat SS, Holladay MW. CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity. Mol Cancer Ther. 2012 Apr;11(4):930-41. doi: 10.1158/1535-7163.MCT-11-0645. Epub 2012 Feb 7. PMID: 22319199.
In vivo protocol: 1. Jiang C, Xie L, Zhang Y, Fujinaga M, Mori W, Kurihara Y, Yamasaki T, Wang F, Zhang MR. Pharmacokinetic Evaluation of [11C]CEP-32496 in Nude Mice Bearing BRAFV600E Mutation-Induced Melanomas. Mol Imaging. 2018 Jan-Dec;17:1536012118795952. doi: 10.1177/1536012118795952. PMID: 30251592; PMCID: PMC6156206. 2. Shimoda Y, Yui J, Fujinaga M, Xie L, Kumata K, Ogawa M, Yamasaki T, Hatori A, Kawamura K, Zhang MR. [(11)C-carbonyl]CEP-32496: radiosynthesis, biodistribution and PET study of brain uptake in P-gp/BCRP knockout mice. Bioorg Med Chem Lett. 2014 Aug 1;24(15):3574-7. doi: 10.1016/j.bmcl.2014.05.045. Epub 2014 Jun 2. PMID: 24930831.

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1: James J, Ruggeri B, Armstrong RC, Rowbottom MW, Jones-Bolin S, Gunawardane RN, Dobrzanski P, Gardner MF, Zhao H, Cramer MD, Hunter K, Nepomuceno RR, Cheng M, Gitnick D, Yazdanian M, Insko DE, Ator MA, Apuy JL, Faraoni R, Dorsey BD, Williams M, Bhagwat SS, Holladay MW. CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity. Mol Cancer Ther. 2012 Apr;11(4):930-41. doi: 10.1158/1535-7163.MCT-11-0645. Epub 2012 Feb 7. PubMed PMID: 22319199.