DB8

4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile

Created:	2011-07-18
Last modified:	2020-06-05

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14 entries where DB8 is found as a standalone ligand

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Chemical Details
Formal Charge	0
Atom Count	65
Chiral Atom Count	0
Bond Count	68
Aromatic Bond Count	17

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Chemical Component Summary
Name	4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
Synonyms	Bosutinib
Systematic Name (OpenEye OEToolkits)	4-[[2,4-bis(chloranyl)-5-methoxy-phenyl]amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
Formula	C₂₆ H₂₉ Cl₂ N₅ O₃
Molecular Weight	530.446
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	ACDLabs	12.01	Clc1c(OC)cc(c(Cl)c1)Nc4c(C#N)cnc3cc(OCCCN2CCN(CC2)C)c(OC)cc34
SMILES	CACTVS	3.370	COc1cc(Nc2c(cnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)C#N)c(Cl)cc1Cl
SMILES	OpenEye OEToolkits	1.7.2	CN1CCN(CC1)CCCOc2cc3c(cc2OC)c(c(cn3)C#N)Nc4cc(c(cc4Cl)Cl)OC
Canonical SMILES	CACTVS	3.370	COc1cc(Nc2c(cnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)C#N)c(Cl)cc1Cl
Canonical SMILES	OpenEye OEToolkits	1.7.2	CN1CCN(CC1)CCCOc2cc3c(cc2OC)c(c(cn3)C#N)Nc4cc(c(cc4Cl)Cl)OC
InChI	InChI	1.03	InChI=1S/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)
InChIKey	InChI	1.03	UBPYILGKFZZVDX-UHFFFAOYSA-N

Drug Info: DrugBank

DrugBank ID	DB06616
Name	Bosutinib
Groups	approved
Description	Bosutinib is a 7-alkoxy-3-quinolinecarbonitrile that functions as a potent, dual SRC and ABL tyrosine kinase inhibitor indicated for chronic myelogenous leukemia (CML), specifically Philadelphia chromosome-positive (Ph+) CML. Philadelphia chromosome is a hallmark of CML due to the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR-ABL fusion protein.[A6902,A261796,A261801] The first BCR-ABL inhibitor, [imatinib], was introduced over a decade ago as a breakthrough in CML management; however, emerging resistance to [imatinib] poses challenges in achieving remission.[A17961] Second-generation BCR-ABL inhibitors like bosutinib inhibit most resistance-conferring BCR-ABL mutations except V299L and T315, thus providing more therapeutic options for patients.[A6901,A17961] Bosutinib was first approved by the FDA in 2012 for the treatment of adult chronic, accelerated, or blast-phase Ph+ CML with resistance or intolerance to prior therapy.[L48436] On September 26, 2023, bosutinib was also approved by the FDA for the treatment of pediatric CML that is newly diagnosed or resistant/intolerant to prior therapy. This approval was based on favorable results obtained from the open-label, randomized, multicenter trial BFORE that showed a significant improvement in major molecular response, defined as a ≤0.1% BCR ABL ratio on an international scale, with bosutinib treatment.[L48441]
Synonyms	4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile Bosutinib monohydrate Bosutinib
Brand Names	Bosulif
Indication	Bosutinib is indicated for the treatment of adult and pediatric patients 1 year of age and older with chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia that is newly diagnosed or resistant or intolerant to prior therapy. It is also indicated for the treatment of adult patients with accelerated or blast phase Philadelphia chromosome-positive chronic myelogenous leukemia that is newly diagnosed or resistant or intolerant to prior therapy.[L48355]
Categories	Amines Antineoplastic Agents Antineoplastic and Immunomodulating Agents Bcr-Abl Tyrosine Kinase Inhibitors Cytochrome P-450 CYP2C8 Inhibitors Cytochrome P-450 CYP2C8 Inhibitors (strength unknown) Cytochrome P-450 CYP2C8 Inhibitors (weak) Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Inhibitors Cytochrome P-450 CYP3A4 Inhibitors (strength unknown) Cytochrome P-450 CYP3A4 Inhibitors (weak) Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Substrates Enzyme Inhibitors Heterocyclic Compounds, Fused-Ring Immunosuppressive Agents Kinase Inhibitor Myelosuppressive Agents Narrow Therapeutic Index Drugs P-glycoprotein inhibitors P-glycoprotein substrates P-glycoprotein substrates with a Narrow Therapeutic Index Protein Kinase Inhibitors Tyrosine Kinase Inhibitors
ATC-Code	L01EA04
CAS number	380843-75-4

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Tyrosine-protein kinase ABL1	MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNS...	unknown	inhibitor
Tyrosine-protein kinase Lyn	MGCIKSKGKDSLSDDGVDLKTQPVRNTERTIYVRDPTSNKQQRPVPESQL...	unknown	inhibitor
Proto-oncogene tyrosine-protein kinase Src	MGSNKSKPKDASQRRRSLEPAENVHGAGGGAFPASQTPSKPASADGHRGP...	unknown	inhibitor
Dual specificity mitogen-activated protein kinase kinase 1	MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRL...	unknown	inhibitor
Dual specificity mitogen-activated protein kinase kinase 2	MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQ...	unknown	inhibitor
Mitogen-activated protein kinase kinase kinase 2	MDDQQALNSIMQDLAVLHKASRPALSLQETRKAKSSSPKKQNDVRVKFEH...	unknown	inhibitor
Calcium/calmodulin-dependent protein kinase type II subunit gamma	MATTATCTRFTDDYQLFEELGKGAFSVVRRCVKKTSTQEYAAKIINTKKL...	unknown	inhibitor
Tyrosine-protein kinase Fgr	MGCVFCKKLEPVATAKEDAGLEGDFRSYGAADHYGPDPTKARPASSFAHI...	unknown	inhibitor
Tyrosine-protein kinase HCK	MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPV...	unknown	inhibitor
Tyrosine-protein kinase Tec	MNFNTILEEILIKRSQQKKKTSPLNYKERLFVLTKSMLTYYEGRAEKKYR...	unknown	inhibitor
STE20-like serine/threonine-protein kinase	MSFFNFRKIFKLGSEKKKKQYEHVKRDLNPEDFWEIIGELGDGAFGKVYK...	unknown	inhibitor
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate,inhibitor
Cytochrome P450 2C8	MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDI...	unknown	inhibitor
P-glycoprotein 1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	unknown	substrate
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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