Details of the Drug

General Information of Drug (ID: DMBSQTR)

Drug Name

Borrelidin

Synonyms

Borrelidin; 7184-60-3; 2-(7-Cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxooxacyclooctadeca-4,6-dien-2-yl)cyclopentanecarboxylic acid; Quinquangulin K 182; Quinquangulin K 031; AC1O53K5; Cyclopentanecarboxylic acid, 2-(7-cyano-8, 16-dihydroxy-9,11,13,15-tetramethyl-18-oxooxacyclooctadeca-4, 6-dien-2-yl)-; 2-[(4Z,6Z)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

489.6

Logarithm of the Partition Coefficient (xlogp)

5.6

Rotatable Bond Count (rotbonds)

2

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

7

Chemical Identifiers

Formula: C28H43NO6
IUPAC Name: (1R,2R)-2-[(2S,4E,6Z,8R,9S,11R,13S,15S,16S)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic acid
Canonical SMILES: C[C@H]1C[C@H](C[C@@H]([C@H](/C(=C\\C=C\\C[C@H](OC(=O)C[C@@H]([C@H](C1)C)O)[C@@H]2CCC[C@H]2C(=O)O)/C#N)O)C)C
InChI: InChI=1S/C28H43NO6/c1-17-12-18(2)14-20(4)27(32)21(16-29)8-5-6-11-25(22-9-7-10-23(22)28(33)34)35-26(31)15-24(30)19(3)13-17/h5-6,8,17-20,22-25,27,30,32H,7,9-15H2,1-4H3,(H,33,34)/b6-5+,21-8-/t17-,18+,19-,20-,22+,23+,24-,25-,27+/m0/s1
InChIKey: OJCKRNPLOZHAOU-UGKRXNSESA-N

Cross-matching ID

PubChem CID: 6436801
CAS Number: 7184-60-3
TTD ID: D03EIM

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Saccharomyces Cell division control protein 28 (Saccha CDC28)	TT75YK4	CDK1_YEAST	Inhibitor	[1]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Drug Response	[2]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[3]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[3]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Gene/Protein Processing	[4]
eIF-2-alpha kinase GCN2 (EIF2AK4)	OTLE1JY8	E2AK4_HUMAN	Gene/Protein Processing	[4]
Eukaryotic translation initiation factor 2A (EIF2A)	OTWXELQP	EIF2A_HUMAN	Post-Translational Modifications	[5]
Threonine--tRNA ligase 1, cytoplasmic (TARS1)	OT0PWST5	SYTC_HUMAN	Gene/Protein Processing	[6]
Vascular endothelial growth factor A, long form	OTIM9MZ3	VEGFA_HUMAN	Gene/Protein Processing	[7]
WW domain-binding protein 4	OT42BLWH	WBP4_HUMAN	Protein Interaction/Cellular Processes	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	Borrelidin inhibits a cyclin-dependent kinase (CDK), Cdc28/Cln2, of Saccharomyces cerevisiae. J Antibiot (Tokyo). 2001 Jan;54(1):84-90.
2	Borrelidin has limited anti-cancer effects in bcl-2 overexpressing breast cancer and leukemia cells and reveals toxicity in non-malignant breast epithelial cells. J Appl Toxicol. 2014 Oct;34(10):1109-13. doi: 10.1002/jat.2946. Epub 2013 Oct 24.
3	Anti-angiogenesis effects of borrelidin are mediated through distinct pathways: threonyl-tRNA synthetase and caspases are independently involved in suppression of proliferation and induction of apoptosis in endothelial cells. J Antibiot (Tokyo). 2003 Aug;56(8):709-15. doi: 10.7164/antibiotics.56.709.
4	Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia. Invest New Drugs. 2012 Aug;30(4):1361-70. doi: 10.1007/s10637-011-9700-y. Epub 2011 Jun 17.
5	Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. Sci Rep. 2015 Aug 14;5:13160. doi: 10.1038/srep13160.
6	Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5508-17. doi: 10.1073/pnas.1405994111. Epub 2014 Dec 8.
7	Borrelidin modulates the alternative splicing of VEGF in favour of anti-angiogenic isoforms. Chem Sci. 2011 Feb 1;2011(2):273-278. doi: 10.1039/C0SC00297F.