Agerafenib

Agerafenib
	The molecular structure of Agerfenib
Names
	IUPAC name 1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea
	Other names CEP-32496; AC013773; Rxdx 105;
Identifiers
CAS Number	1188910-76-0;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL2029988;
ChemSpider	28506650;
DrugBank	DB15068;
IUPHAR/BPS	7880;
PubChem CID	56846693;
UNII	78I4VEX88N;
CompTox Dashboard (EPA)	DTXSID601025976 ;
	InChI 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) Key: DKNUPRMJNUQNHR-UHFFFAOYSA-N;
	SMILES CC(C)(C1=CC(=NO1)NC(=O)NC2=CC(=CC=C2)OC3=NC=NC4=CC(=C(C=C43)OC)OC)C(F)(F)F;
Properties
Chemical formula	C24H22F3N5O5
Molar mass	517.5 g/mol
Solubility in water	≥ 25.85mg/mL in DMSO
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Agerafenib is a selective multi-kinase inhibitor. It is undergoing a trial to test its ability to treat malignant tumors in humans. It is effective in doses ranging between 30 milligrams and 100 milligrams. It is also known as CEP-32496 and RXDX 105. It is a strong inhibitor of the BRAF gene that is commonly found in cancerous cells.

Discovery

Agerafenib was originally discovered by a company called Daiichi Sankyo (then called Ambit Biosciences) and Teva Pharmaceuticals (then called Cephalon) during a research program.^[1] The chemical was originally named "CEP-32496" before being renamed to "RXDX 105" in 2015.^[1] It is currently undergoing a clinical trial to test its effectiveness against cancer in humans.^[2]

Characteristics

Agerafenib's chemical formula consists of 24 carbon atoms, 22 hydrogen atoms, 3 fluorine atoms, 5 nitrogen atoms and 5 oxygen atoms.^[3] The chemical's molar mass is 517.465 g/mol, and the monoisotopic mass is 517.157303 g/mol.^[4] It appears as a white to off-white crystalline powder in room temperature.^[5] Agerafenib has 5 hydrogen bond acceptors and 2 hydrogen bond donors.^[6] It has an partition coefficient of 4.35. It has 10 rotatable bonds and a topological polar surface area of 120.63.^[6]

The chemical is a strong inhibitor of the BRAF gene, which is present in around 7% of all malignant tumors.^[7] It does this due to its strong cytotoxicity to cells containing it.^[7] Agerafenib also inhibits phosphorylation in mitogen-activated protein kinase (an enzyme that causes certain cellular responses).^[8] The drug is shown to be most effective in humans in doses between 30 milligrams and 100 milligrams.^[9]

References

^ ^a ^b "NCATS Inxight Drugs — AGERAFENIB". National Center for Advancing Translational Sciences. Archived from the original on 2025-04-15. Retrieved 2025-06-25.
^ "Agerafenib". DrugBank. Archived from the original on 2025-04-12. Retrieved 2025-06-25.
^ "CEP-32496". Good Laboratory Practice Bioscience. Archived from the original on 2025-06-25. Retrieved 2025-06-25.
^ "Comptox – 1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea". United States Environmental Protection Agency. Retrieved 2025-06-25.
^ Ruggeri, B.; Wabler, M.; Bruckheimer, E.; Wilkinson, B.; Dorsey, B.; Trusko, S.; Friedman, J. (2014). "471 Screening of Champions predictive TumorGraft platform guides the clinical development of the selective dual BRAF-EGFR inhibitor CEP-32496". European Journal of Cancer. 50: 154. doi:10.1016/S0959-8049(14)70597-0.
^ ^a ^b "agerafenib | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY". Guide to Pharmocology. Retrieved 2025-06-26.
^ ^a ^b James, Joyce; Ruggeri, Bruce; Armstrong, Robert C.; Rowbottom, Martin W.; Jones-Bolin, Susan; Gunawardane, Ruwanthi N.; Dobrzanski, Pawel; Gardner, Michael F.; Zhao, Hugh; Cramer, Merryl D.; Hunter, Kathryn; Nepomuceno, Ronald R.; Cheng, Mangeng; Gitnick, Dana; Yazdanian, Mehran (2012-04-01). "CEP-32496: A Novel Orally Active BRAFV600E Inhibitor with Selective Cellular and In Vivo Antitumor Activity". Molecular Cancer Therapeutics. 11 (4): 930–941. doi:10.1158/1535-7163.MCT-11-0645. ISSN 1535-7163. PMID 22319199.
^ Jiang, Cuiping; Xie, Lin; Zhang, Yiding; Fujinaga, Masayuki; Mori, Wakana; Kurihara, Yusuke; Yamasaki, Tomoteru; Wang, Feng; Zhang, Ming-Rong (2018-01-01). "Pharmacokinetic Evaluation of [ 11 C]CEP-32496 in Nude Mice Bearing BRAF V600E Mutation-Induced Melanomas". Molecular Imaging. 17. doi:10.1177/1536012118795952. ISSN 1535-3508. PMC 6156206. PMID 30251592.
^ Purich, Daniel (2017). The Inhibitor Index: A Desk Reference on Enzyme Inhibitors, Receptor Antagonists, Drugs, Toxins, Poisons, Biologics, and Therapeutic Leads. London: CRC Press. p. 1989. ISBN 978-1-351-73067-9.

[:0-1] "NCATS Inxight Drugs — AGERAFENIB". National Center for Advancing Translational Sciences. Archived from the original on 2025-04-15. Retrieved 2025-06-25.

[2] "Agerafenib". DrugBank. Archived from the original on 2025-04-12. Retrieved 2025-06-25.

[3] "CEP-32496". Good Laboratory Practice Bioscience. Archived from the original on 2025-06-25. Retrieved 2025-06-25.

[4] "Comptox – 1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea". United States Environmental Protection Agency. Retrieved 2025-06-25.

[5] Ruggeri, B.; Wabler, M.; Bruckheimer, E.; Wilkinson, B.; Dorsey, B.; Trusko, S.; Friedman, J. (2014). "471 Screening of Champions predictive TumorGraft platform guides the clinical development of the selective dual BRAF-EGFR inhibitor CEP-32496". European Journal of Cancer. 50: 154. doi:10.1016/S0959-8049(14)70597-0.

[:2-6] "agerafenib | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY". Guide to Pharmocology. Retrieved 2025-06-26.

[:1-7] James, Joyce; Ruggeri, Bruce; Armstrong, Robert C.; Rowbottom, Martin W.; Jones-Bolin, Susan; Gunawardane, Ruwanthi N.; Dobrzanski, Pawel; Gardner, Michael F.; Zhao, Hugh; Cramer, Merryl D.; Hunter, Kathryn; Nepomuceno, Ronald R.; Cheng, Mangeng; Gitnick, Dana; Yazdanian, Mehran (2012-04-01). "CEP-32496: A Novel Orally Active BRAFV600E Inhibitor with Selective Cellular and In Vivo Antitumor Activity". Molecular Cancer Therapeutics. 11 (4): 930–941. doi:10.1158/1535-7163.MCT-11-0645. ISSN 1535-7163. PMID 22319199.

[8] Jiang, Cuiping; Xie, Lin; Zhang, Yiding; Fujinaga, Masayuki; Mori, Wakana; Kurihara, Yusuke; Yamasaki, Tomoteru; Wang, Feng; Zhang, Ming-Rong (2018-01-01). "Pharmacokinetic Evaluation of [ 11 C]CEP-32496 in Nude Mice Bearing BRAF V600E Mutation-Induced Melanomas". Molecular Imaging. 17. doi:10.1177/1536012118795952. ISSN 1535-3508. PMC 6156206. PMID 30251592.

[9] Purich, Daniel (2017). The Inhibitor Index: A Desk Reference on Enzyme Inhibitors, Receptor Antagonists, Drugs, Toxins, Poisons, Biologics, and Therapeutic Leads. London: CRC Press. p. 1989. ISBN 978-1-351-73067-9.

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