WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205903
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.
Hodoodo Cat#: H205903
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
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: | Agerafenib (CEP-32496; RXDX-105) is an efficacious inhibitor of BRAFV600E with a Kd of 14 nM. |
| In vitro activity: | RXDX-105 is a potent inhibitor of multiple kinases, including the RET and BRAF kinases (Figure 1) To investigate whether RXDX-105 is able to inhibit the RET kinase and the RAS-MAPK pathway in neuroblastoma cells, this study evaluated a panel of neuroblastoma cell lines for RET, MEK, and ERK expression and phosphorylation after 24 hours of treatment with RXDX-105. RET phosphorylation was inhibited with RXDX-105 treatment in a dose dependent manner, while levels of total RET remained relatively stable. RET phosphorylation was also increased after the addition of 5 μM 13-cis-retinoic acid, which was also inhibited by RXDX-105 (Figure 4). RXDX-105 treatment also resulted in significantly decreased MEK and ERK phosphorylation, while levels of total ERK remained the same or slightly increased (Figure 4, Supplementary Figure 1). Reference: Oncotarget. 2019 Oct 29; 10(59): 6323–6333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824878/ |
| In vivo activity: | Inhibition of MEK phosphorylation in BRAFV600E-positive subcutaneous Colo-205 tumor xenografts in nude mice was detected following administration of CEP-32496 (10, 30, and 55 mg/kg orally twice daily; Fig. 4A). CEP-32496 at 10 and 30 mg/kg resulted in significant (P < 0.03) inhibition of normalized pMEK in tumor lysates relative to vehicle controls at 2 and 6 hours but returned to baseline by 10 hours, whereas a 55 mg/kg dose resulted in a 75% to 57% (P < 0.03) inhibition of pMEK at 2 though 10-hour postadministration, with normalization to baseline by 24 hours. Reference: Mol Imaging. 2018 Jan-Dec;17:1536012118795952. https://mct.aacrjournals.org/content/11/4/930.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 26.3 | 50.88 | |
| DMF | 10.0 | 19.32 | |
| DMF:PBS (pH 7.2) (1:2) | 0.3 | 0.58 | |
| Ethanol | 2.0 | 3.86 |
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.
| 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. Li GG, Somwar R, Joseph J, Smith RS, Hayashi T, Martin L, Franovic A, Schairer A, Martin E, Riely GJ, Harris J, Yan S, Wei G, Oliver JW, Patel R, Multani P, Ladanyi M, Drilon A. Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations. Clin Cancer Res. 2017 Jun 15;23(12):2981-2990. doi: 10.1158/1078-0432.CCR-16-1887. Epub 2016 Dec 23. PMID: 28011461; PMCID: PMC5477238. |
| 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. Li GG, Somwar R, Joseph J, Smith RS, Hayashi T, Martin L, Franovic A, Schairer A, Martin E, Riely GJ, Harris J, Yan S, Wei G, Oliver JW, Patel R, Multani P, Ladanyi M, Drilon A. Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations. Clin Cancer Res. 2017 Jun 15;23(12):2981-2990. doi: 10.1158/1078-0432.CCR-16-1887. Epub 2016 Dec 23. PMID: 28011461; PMCID: PMC5477238. |
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.
