Details of the Drug

General Information of Drug (ID: DMVR628)

Drug Name
Vindesine
Synonyms
DAVA; Vindesin; Vindesina; Vindesinum; Desacetylvinblastine amide; Lilly 112531; Vindesina [INN-Spanish]; Vindesinum [INN-Latin]; Vindesine (USAN/INN); Vindesine [USAN:BAN:INN]; Vindesine [USAN:INN:BAN]; 3-(Aminocarbonyl)-O(sup 4)-deacetyl-3-de(methoxycarbonyl)vincaleukoblastine; 3-(aminocarbonyl)-O(4)-deacetyl-3-de(methoxycarbonyl)vincaleukoblastine; 3-Carbamoyl-4-deacetyl-3-de(methoxycarbonyl)vincaleukoblastine; 3-carbamoyl-O(4)-deacetyl-3-de(methoxycarbonyl)vincaleukoblastine; Methyl (5S,7S,9S)-9-[(2b,3b,4b,5a,12b,19a)-3-carbamoyl-3,4-dihydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidin-15-yl]-5-ethyl-5-hydroxy-1,4,5,6,7,8,9,10-octahydro-2H-3,7-methanoazacycloundecino[5,4-b]indole-9-carboxylate; Methyl (5S,7S,9S)-9-[(2beta,3beta,4beta,5alpha,12beta,19alpha)-3-carbamoyl-3,4-dihydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidin-15-yl]-5-ethyl-5-hydroxy-1,4,5,6,7,8,9,10-octahydro-2H-3,7-methanoazacycloundecino[5,4-b]indole-9-carboxylate
Indication
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [1]
Chronic myelogenous leukaemia 2A20.0 Approved [2]
Lung cancer 2C25.0 Approved [3]
Melanoma 2C30 Approved [4]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 753.9
Logarithm of the Partition Coefficient (xlogp) 2.7
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 5
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
Clearance
The drug present in the plasma can be removed from the body at the rate of 2.2 mL/min/kg [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 24 hours [5]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.14325 micromolar/kg/day [6]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 5 L/kg [5]
Chemical Identifiers
Formula
C43H55N5O7
IUPAC Name
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-carbamoyl-12-ethyl-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraene-13-carboxylate
Canonical SMILES
CC[C@@]1(C[C@@H]2C[C@@](C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)[C@]78CCN9[C@H]7[C@@](C=CC9)([C@H]([C@@]([C@@H]8N6C)(C(=O)N)O)O)CC)OC)C(=O)OC)O
InChI
InChI=1S/C43H55N5O7/c1-6-39(52)21-25-22-42(38(51)55-5,33-27(13-17-47(23-25)24-39)26-11-8-9-12-30(26)45-33)29-19-28-31(20-32(29)54-4)46(3)35-41(28)15-18-48-16-10-14-40(7-2,34(41)48)36(49)43(35,53)37(44)50/h8-12,14,19-20,25,34-36,45,49,52-53H,6-7,13,15-18,21-24H2,1-5H3,(H2,44,50)/t25-,34+,35-,36-,39+,40-,41-,42+,43+/m1/s1
InChIKey
HHJUWIANJFBDHT-KOTLKJBCSA-N
Cross-matching ID
PubChem CID
40839
ChEBI ID
CHEBI:36373
CAS Number
53643-48-4
DrugBank ID
DB00309
TTD ID
D04RLY
VARIDT ID
DR00397
INTEDE ID
DR1693
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Tubulin beta (TUBB) TTYFKSZ NOUNIPROTAC Binder [7]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [10]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [10]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [11]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2 Vindesine in the treatment of leukaemia. Leuk Lymphoma. 1997 Aug;26(5-6):497-506.
3 Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010 Aug 10;28(23):3739-45.
4 Study of therapy resistance in cancer cells with functional proteome analysis. Clin Chem Lab Med. 2002 Mar;40(3):221-34.
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7 Antiproliferating activity of the mitotic inhibitor pironetin against vindesine- and paclitaxel-resistant human small cell lung cancer H69 cells. Anticancer Res. 2007 Mar-Apr;27(2):729-36.
8 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
9 Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem Pharmacol. 1993 Feb 24;45(4):853-61.
10 Structural perspectives of the CYP3A family and their small molecule modulators in drug metabolism. 2019, 3(3), 132-142.
11 The growth-inhibition effect of tamoxifen in the combination chemotherapeutics on the human cholangiocarcinoma cell line QBC939. Mol Biol Rep. 2010 Jul;37(6):2693-701. doi: 10.1007/s11033-009-9801-2. Epub 2009 Sep 13.