QKM

4-{2-[(2R,3R)-3-(2,5-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-1,3-thiazol-4-yl}benzonitrile

Created:	2019-11-07
Last modified:	2021-03-01

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1 entries where QKM is found as a standalone ligand

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Chemical Details
Formal Charge	0
Atom Count	48
Chiral Atom Count	2
Bond Count	51
Aromatic Bond Count	22

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Chemical Component Summary
Name	4-{2-[(2R,3R)-3-(2,5-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-1,3-thiazol-4-yl}benzonitrile
Synonyms	Isavuconazole
Systematic Name (OpenEye OEToolkits)	4-[2-[(2~{R},3~{R})-3-[2,5-bis(fluoranyl)phenyl]-3-oxidanyl-4-(1,2,4-triazol-1-yl)butan-2-yl]-1,3-thiazol-4-yl]benzenecarbonitrile
Formula	C₂₂ H₁₇ F₂ N₅ O S
Molecular Weight	437.465
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	ACDLabs	12.01	CC(C(c1c(ccc(c1)F)F)(Cn2ncnc2)O)c4nc(c3ccc(cc3)C#N)cs4
SMILES	CACTVS	3.385	C[CH](c1scc(n1)c2ccc(cc2)C#N)[C](O)(Cn3cncn3)c4cc(F)ccc4F
SMILES	OpenEye OEToolkits	2.0.7	CC(c1nc(cs1)c2ccc(cc2)C#N)C(Cn3cncn3)(c4cc(ccc4F)F)O
Canonical SMILES	CACTVS	3.385	C[C@@H](c1scc(n1)c2ccc(cc2)C#N)[C@](O)(Cn3cncn3)c4cc(F)ccc4F
Canonical SMILES	OpenEye OEToolkits	2.0.7	C[C@@H](c1nc(cs1)c2ccc(cc2)C#N)[C@](Cn3cncn3)(c4cc(ccc4F)F)O
InChI	InChI	1.03	InChI=1S/C22H17F2N5OS/c1-14(21-28-20(10-31-21)16-4-2-15(9-25)3-5-16)22(30,11-29-13-26-12-27-29)18-8-17(23)6-7-19(18)24/h2-8,10,12-14,30H,11H2,1H3/t14-,22+/m0/s1
InChIKey	InChI	1.03	DDFOUSQFMYRUQK-RCDICMHDSA-N

Drug Info: DrugBank

DrugBank ID	DB11633
Name	Isavuconazole
Groups	approved investigational
Description	Isavuconazole is an triazole antifungal with broad spectrum of activity and good safety profile [A32026]. It is approved by the FDA and EMA for the treatment of invasive aspergillosis and mucormycosis. It works by inhibiting fungal cell membrane synthesis. Invasive fungal infections pose significant clinical challenges for patients, especially those who are immunocompromised. In vitro, most of the _Candida_ species, most _Aspergillus_ species, Mucorales, _Cryptococcus_ spp., _Fusarium_ species, dermatophytes and dimorphic fungi displayed susceptibility to isavuconzaole [A32029]. Resistance to isavuconazole has been associated with the mutation in the target gene CYP51 [FDA Label]. Cross-resistance between isavuconazole and other azoles was also proposed although the clinical relevance is unclear [FDA Label]. As isavuconazole displays low water solubility, it is found as an active ingredient of its prodrug, [DB06636]. The prodrug formulation of isavuconazole is FDA- and EMA-approved and is marketed under the trade name Cresemba for the treatment of invasive aspergillosis and mucormycosis as oral or intravenous administration. The intravenous formulation is cyclodextrin-free which gives isavuconazole an advantage over other azole antifungals that requires cyclodextrin for facilitating drug solubility; this is because cyclodextrin has a potential for nephrotoxicity [A32029]. It is proposed that the intravenous and oral dosing can be used interchangeably [L1482], without the need for a repeat loading dose when transitioning from an IV to an oral formulation [A32026]. Isavuconazonium displays excellent water solubility for intravenous formulations, good absorption, and enhanced oral bioavailability [A32026]. Following administration, isavuconazonium undergoes biotransformation to form the active moiety, isavuconazole, for the antifungal actions.
Synonyms	Isavuconazole isavuconazol isavuconazolum
Brand Names	Cresemba
Indication	- Indicated for patients 18 years of age and older for the treatment of invasive aspergillosis [FDA Label]. - Indicated for patients 18 years of age and older for the treatment of invasive mucormycosis [FDA Label], including patients where treatment amphotericin B is inappropriate [L1482].
Categories	Anti-Infective Agents Antifungal Agents Antiinfectives for Systemic Use Antimycotics for Systemic Use Azole Antifungals BCRP/ABCG2 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 CYP2B6 Inducers (weak) Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2C19 inhibitors (strength unknown) Cytochrome P-450 CYP2C8 Inducers Cytochrome P-450 CYP2C8 Inducers (weak) Cytochrome P-450 CYP2C8 Inhibitors Cytochrome P-450 CYP2C8 Inhibitors (strength unknown) Cytochrome P-450 CYP2C9 Inducers Cytochrome P-450 CYP2C9 Inducers (weak) Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 CYP2C9 Inhibitors (strength unknown) Cytochrome P-450 CYP2D6 Inhibitors Cytochrome P-450 CYP2D6 Inhibitors (strength unknown) Cytochrome P-450 CYP3A Inducers Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Inducers Cytochrome P-450 CYP3A4 Inducers (weak) Cytochrome P-450 CYP3A4 Inhibitors Cytochrome P-450 CYP3A4 Inhibitors (moderate) Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A4 Substrates (strength unknown) Cytochrome P-450 CYP3A5 Inhibitors Cytochrome P-450 CYP3A5 Inhibitors (moderate) Cytochrome P-450 CYP3A5 Substrates Cytochrome P-450 Enzyme Inducers Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Substrates Isavuconazole and Prodrugs OCT2 Inhibitors P-glycoprotein inhibitors Triazole and tetrazole derivatives Triazole Derivatives UGT1A9 Inhibitors
ATC-Code	J02AC05
CAS number	241479-67-4

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Lanosterol 14-alpha demethylase	MSTENTSLVVELLEYVKLGLSYFQALPLAQRVSIMVALPFVYTITWQLLY...	unknown	inhibitor
Potassium voltage-gated channel subfamily H member 2	MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCE...	unknown	inhibitor
Voltage-dependent L-type calcium channel subunit alpha-1C	MVNENTRMYIPEENHQGSNYGSPRPAHANMNANAAAGLAPEHIPTPGAAL...	unknown	inhibitor
G protein-activated inward rectifier potassium channel 2	MAKLTESMTNVLEGDSMDQDVESPVAIHQPKLPKQARDDLPRHISRDRTK...	unknown	inhibitor
G protein-activated inward rectifier potassium channel 3	MAQENAAFSPGQEEPPRRRGRQRYVEKDGRCNVQQGNVRETYRYLTDLFT...	unknown	inhibitor
ATP-sensitive inward rectifier potassium channel 11	MLSRKGIIPEEYVLTRLAEDPAEPRYRARQRRARFVSKKGNCNVAHKNIR...	unknown	inhibitor
Potassium voltage-gated channel subfamily A member 5	MEIALVPLENGGAMTVRGGDEARAGCGQATGGELQCPPTAGLSDGPKEPA...	unknown	inhibitor
Potassium voltage-gated channel subfamily D member 3	MAAGVAAWLPFARAAAIGWMPVANCPMPLAPADKNKRQDELIVLNVSGRR...	unknown	inhibitor
Potassium voltage-gated channel subfamily KQT member 1	MAAASSPPRAERKRWGWGRLPGARRGSAGLAKKCPFSLELAEGGPAGGAL...	unknown	inhibitor
Sodium channel protein type 5 subunit alpha	MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEE...	unknown	inhibitor
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate,inhibitor,inducer
Cytochrome P450 3A5	MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNV...	unknown	substrate,inhibitor
Cytochrome P450 2C8	MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDI...	unknown	inhibitor,inducer
Cytochrome P450 2C9	MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDI...	unknown	inhibitor,inducer
Cytochrome P450 2C19	MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDV...	unknown	inhibitor
Cytochrome P450 2D6	MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVD...	unknown	inhibitor
Cytochrome P450 2B6	MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRG...	unknown	inducer
UDP-glucuronosyltransferase 1-9	MACTGWTSPLPLCVCLLLTCGFAEAGKLLVVPMDGSHWFTMRSVVEKLIL...	unknown	inhibitor
UDP-glucuronosyltransferase 1-8	MARTGWTSPIPLCVSLLLTCGFAEAGKLLVVPMDGSHWFTMQSVVEKLIL...	unknown	inhibitor
P-glycoprotein 1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	unknown	inhibitor
ATP-binding cassette sub-family G member 2	MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKS...	unknown	inhibitor
Solute carrier family 22 member 2	MPTTVDDVLEHGGEFHFFQKQMFFLLALLSATFAPIYVGIVFLGFTPDHR...	unknown	inhibitor
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Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682