Cobimetinib information

Cobimetinib
Clinical data
Pronunciation	/ˌkoʊbɪˈmɛtɪnɪb/ KOH-bim-ET-i-nib
Trade names	Cotellic
Other names	GDC-0973, XL-518
AHFS/Drugs.com	Monograph
MedlinePlus	a615057
License data	US DailyMed: Cobimetinib;
Pregnancy; category	AU: D; ;
Routes of; administration	By mouth
ATC code	L01EE02 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only; EU: Rx-only; In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	reported from 28% to 46%
Protein binding	95%
Metabolism	Intestinal and low Liver clearance (mostly CYP3A4 oxidation and UGT2B7 glucuronidation)
Elimination half-life	44 hours (mean)
Excretion	Feces (76–77%), urine (17.9–18%) (after oral and IV administration)
Identifiers
	IUPAC name (S)-[3,4-Difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl] methanone;
CAS Number	934660-93-2;
PubChem CID	16222096;
IUPHAR/BPS	7626;
DrugBank	DB05239 ;
ChemSpider	17349374;
UNII	ER29L26N1X;
KEGG	D10405; D10615;
ChEBI	CHEBI:90851 ;
ChEMBL	ChEMBL2146883;
CompTox Dashboard (EPA)	DTXSID60239435 ;
Chemical and physical data
Formula	C21H21F3IN3O2
Molar mass	531.318 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CCN[C@@H](C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O;
	InChI InChI=1S/C21H21F3IN3O2/c22-14-6-5-13(19(18(14)24)27-16-7-4-12(25)9-15(16)23)20(29)28-10-21(30,11-28)17-3-1-2-8-26-17/h4-7,9,17,26-27,30H,1-3,8,10-11H2/t17-/m0/s1; Key:BSMCAPRUBJMWDF-KRWDZBQOSA-N;

Cobimetinib, sold under the brand name Cotellic, is an anti-cancer medication used in combination with vemurafenib (Zelboraf) alone or with both vemurafenib and atezolizumab (Tecentriq) to treat melanoma.^[2]^[8] Cobimetinib is a MEK inhibitor.^[2] Cotellic, Zelboraf, and Tecentriq are all marketed by Genentech.^[2]^[8]^[9]

The most common side effects include diarrhea, rash, nausea (feeling sick), vomiting, pyrexia (fever), photosensitivity (light sensitivity) reaction, abnormal results for certain liver function tests (increased levels of alanine aminotransferase, aspartate aminotransferase) and abnormal results for an enzyme related to muscle breakdown (creatine phosphokinase).^[5]

Cobimetinib was approved for medical use in the United States in November 2015.^[10]^[11]

^ ^a ^b "Products". guildlink.com.au.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Cotellic- cobimetinib tablet, film coated". DailyMed. 5 November 2019. Retrieved 19 October 2020.
^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
^ "Health Canada New Drug Authorizations: 2016 Highlights". Health Canada. 14 March 2017. Retrieved 7 April 2024.
^ ^a ^b Cite error: The named reference Cotellic EPAR was invoked but never defined (see the help page).
^ ^a ^b Takahashi RH, Choo EF, Ma S, Wong S, Halladay J, Deng Y, et al. (January 2016). "Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans". Drug Metabolism and Disposition. 44 (1): 28–39. doi:10.1124/dmd.115.066282. PMID 26451002.
^ Choo E, Takahashi R, Rooney I, Gates M, Deng A, Musib L (January 30, 2014). "Abstract B160: Assessing Human Absorption, Metabolism, Routes of Excretion and the Contribution of Intestinal Metabolism to the Oral Clearance of Cobimetinib, a MEK Inhibitor". Molecular Cancer Therapeutics. 12 (11 Supplement): B160. doi:10.1158/1535-7163.TARG-13-B160.
^ ^a ^b "Tecentriq- atezolizumab injection, solution". DailyMed. Retrieved 21 September 2021.
^ "Zelboraf- vemurafenib tablet, film coated". DailyMed. Retrieved 21 September 2021.
^ "Cotellic (cobimetinib) tablet". U.S. Food and Drug Administration (FDA). 8 December 2015. Retrieved 21 September 2021.
^ "Drug Trials Snapshots: Cotellic". U.S. Food and Drug Administration (FDA). 30 July 2020. Retrieved 21 September 2021. This article incorporates text from this source, which is in the public domain.

[Cotellic_PI-1] "Products". guildlink.com.au.

[Cotellic_FDA_label-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Cotellic- cobimetinib tablet, film coated". DailyMed. 5 November 2019. Retrieved 19 October 2020.

[3] "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.

[4] "Health Canada New Drug Authorizations: 2016 Highlights". Health Canada. 14 March 2017. Retrieved 7 April 2024.

[Cotellic_EPAR-5] Cite error: The named reference Cotellic EPAR was invoked but never defined (see the help page).

[Takahashi-6] Takahashi RH, Choo EF, Ma S, Wong S, Halladay J, Deng Y, et al. (January 2016). "Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans". Drug Metabolism and Disposition. 44 (1): 28–39. doi:10.1124/dmd.115.066282. PMID 26451002.

[Choo-7] Choo E, Takahashi R, Rooney I, Gates M, Deng A, Musib L (January 30, 2014). "Abstract B160: Assessing Human Absorption, Metabolism, Routes of Excretion and the Contribution of Intestinal Metabolism to the Oral Clearance of Cobimetinib, a MEK Inhibitor". Molecular Cancer Therapeutics. 12 (11 Supplement): B160. doi:10.1158/1535-7163.TARG-13-B160.

[Tecentriq_FDA_label-8] "Tecentriq- atezolizumab injection, solution". DailyMed. Retrieved 21 September 2021.

[Zelboraf_FDA_label-9] "Zelboraf- vemurafenib tablet, film coated". DailyMed. Retrieved 21 September 2021.

[10] "Cotellic (cobimetinib) tablet". U.S. Food and Drug Administration (FDA). 8 December 2015. Retrieved 21 September 2021.

[FDA_snapshot-11] "Drug Trials Snapshots: Cotellic". U.S. Food and Drug Administration (FDA). 30 July 2020. Retrieved 21 September 2021. This article incorporates text from this source, which is in the public domain.

Cobimetinib information

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Clinical data

Pronunciation	/ˌkoʊbɪˈmɛtɪnɪb/ KOH-bim-ET-i-nib
Trade names	Cotellic
Other names	GDC-0973, XL-518
AHFS/Drugs.com	Monograph
MedlinePlus	a615057
License data	US DailyMed: Cobimetinib
Pregnancy category	AU: D^[1]
Routes of administration	By mouth^[2]
ATC code	L01EE02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)^[1]^[3] CA: ℞-only^[4] UK: POM (Prescription only) US: ℞-only^[2] EU: Rx-only^[5] In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	reported from 28%^[6] to 46%^[2]
Protein binding	95%^[2]
Metabolism	Intestinal and low Liver clearance (mostly CYP3A4 oxidation and UGT2B7 glucuronidation)^[2]^[6]
Elimination half-life	44 hours (mean)^[2]
Excretion	Feces (76–77%), urine (17.9–18%) (after oral and IV administration)^[2]^[7]
Identifiers
IUPAC name (S)-[3,4-Difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl] methanone
CAS Number	934660-93-2
PubChem CID	16222096
IUPHAR/BPS	7626
DrugBank	DB05239^Y
ChemSpider	17349374
UNII	ER29L26N1X
KEGG	D10405 D10615
ChEBI	CHEBI:90851^Y
ChEMBL	ChEMBL2146883
CompTox Dashboard (EPA)	DTXSID60239435
Chemical and physical data
Formula	C₂₁H₂₁F₃IN₃O₂
Molar mass	531.318 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C1CCN[C@@H](C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O
InChI InChI=1S/C21H21F3IN3O2/c22-14-6-5-13(19(18(14)24)27-16-7-4-12(25)9-15(16)23)20(29)28-10-21(30,11-28)17-3-1-2-8-26-17/h4-7,9,17,26-27,30H,1-3,8,10-11H2/t17-/m0/s1 Key:BSMCAPRUBJMWDF-KRWDZBQOSA-N