Details of the Drug

General Information of Drug (ID: DMYH9SU)

Drug Name
Batrachotoxin
Synonyms
BATRACHOTOXIN; UNII-TSG6XHX09R; TSG6XHX09R; Batrachotoxinin A, 20-(2,4-dimethyl-1H-pyrrole-3-carboxylate); Betrachotoxinin A, 20-alpha-(2,4-dimethyl-1H-pyrrole-3-carboxylate); 23509-16-2; GTPL2619; LS-24727; Betrachotoxinin A, 20-alpha-(2,4-dimethyl-1H-pyrrole-3-carboxylate) (9CI)
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 538.7
Topological Polar Surface Area (xlogp) 1.6
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C31H42N2O6
IUPAC Name
[(1S)-1-[(1R,5R,6S,9R,11S,12R,14R)-9,12-dihydroxy-6,16-dimethyl-10,19-dioxa-16-azahexacyclo[12.5.3.15,9.01,14.02,11.06,11]tricosa-2,21-dien-22-yl]ethyl] 2,4-dimethyl-1H-pyrrole-3-carboxylate
Canonical SMILES
CC1=CNC(=C1C(=O)O[C@@H](C)C2=CC[C@@]34[C@@]2(C[C@H]([C@@]56C3=CC[C@H]7[C@@]5(CC[C@](C7)(O6)O)C)O)CN(CCO4)C)C
InChI
InChI=1S/C31H42N2O6/c1-18-16-32-19(2)25(18)26(35)38-20(3)22-8-9-30-23-7-6-21-14-29(36)11-10-27(21,4)31(23,39-29)24(34)15-28(22,30)17-33(5)12-13-37-30/h7-8,16,20-21,24,32,34,36H,6,9-15,17H2,1-5H3/t20-,21+,24+,27-,28-,29+,30-,31-/m0/s1
InChIKey
ISNYUQWBWALXEY-OMIQOYQYSA-N
Cross-matching ID
PubChem CID
6324647
CAS Number
23509-16-2
TTD ID
D0G9WE
VARIDT ID
DR01019

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
SCN1A messenger RNA (SCN1A mRNA) TTANOZH SCN1A_HUMAN Activator [2]
Voltage-gated sodium channel alpha Nav1.2 (SCN2A) TTLJTUF SCN2A_HUMAN Activator [3]
Voltage-gated sodium channel alpha Nav1.3 (SCN3A) TTAXZ0K SCN3A_HUMAN Activator [4]
Voltage-gated sodium channel alpha Nav1.4 (SCN4A) TT84DRB SCN4A_HUMAN Activator [5]
Voltage-gated sodium channel alpha Nav1.5 (SCN5A) TTZOVE0 SCN5A_HUMAN Activator [6]
Voltage-gated sodium channel alpha Nav1.6 (SCN8A) TT54ERL SCN8A_HUMAN Activator [7]
Voltage-gated sodium channel alpha Nav1.7 (SCN9A) TT4G2JS SCN9A_HUMAN Activator [8]
Voltage-gated sodium channel alpha Nav1.8 (SCN10A) TT90XZ8 SCNAA_HUMAN Activator [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2619).
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 578).
3 Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13947-52.
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 580).
5 Point mutations in segment I-S6 render voltage-gated Na+ channels resistant to batrachotoxin. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2653-8.
6 Binding of [3H]batrachotoxinin A benzoate to specific sites on rat cardiac sodium channels. Mol Pharmacol. 1986 Dec;30(6):617-23.
7 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 583).
8 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 584).
9 The poison Dart frog's batrachotoxin modulates Nav1.8. FEBS Lett. 2004 Nov 5;577(1-2):245-8.
10 Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels. J Pharmacol Exp Ther. 2005 Dec;315(3):1237-46.
11 Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707.
12 3-(4-phenoxyphenyl)pyrazoles: a novel class of sodium channel blockers. J Med Chem. 2004 Mar 11;47(6):1547-52.
13 Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J Biol Chem. 2007 Oct 19;282(42):30699-706.
14 Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker. Pain. 2012 Jan;153(1):80-5.
15 Primary erythromelalgia: a review. Orphanet J Rare Dis. 2015 Sep 30;10:127.
16 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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19 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800041740)
20 Binding of batrachotoxinin A 20-alpha-benzoate to a receptor site associated with sodium channels in synaptic nerve ending particles. J Biol Chem. 1981 Sep 10;256(17):8922-7.
21 Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68.
22 Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9.
23 Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J Med Chem. 2001 Jan 18;44(2):115-37.
24 Halothane attenuates the cerebroprotective action of several Na+ and Ca2+ channel blockers via reversal of their ion channel blockade. Eur J Pharmacol. 2002 Oct 4;452(2):175-81.
25 Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12.
26 From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials. Am J Cardiol. 1996 Aug 29;78(4A):28-33.
27 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
28 Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian senso... J Biol Chem. 2004 Jun 11;279(24):25774-82.
29 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
30 Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
31 Heterologous expression and functional analysis of rat Nav1.8 (SNS) voltage-gated sodium channels in the dorsal root ganglion neuroblastoma cell line ND7-23. Neuropharmacology. 2004 Mar;46(3):425-38.
32 Pathobiology of visceral pain: molecular mechanisms and therapeutic implications. II. Genetic approaches to pain therapy. Am J Physiol Gastrointest Liver Physiol. 2000 Apr;278(4):G507-12.
33 Oral Administration of PF-01247324, a Subtype-Selective Nav1.8 Blocker, Reverses Cerebellar Deficits in a Mouse Model of Multiple Sclerosis. PLoS One. 2015; 10(3): e0119067.
34 Substituted benzamides and methods of use thereof. US9694002.
35 The TTX metabolite 4,9-anhydro-TTX is a highly specific blocker of the Na(v1.6) voltage-dependent sodium channel. Am J Physiol Cell Physiol. 2007 Aug;293(2):C783-9.
36 Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers. J Med Chem. 1994 Jan 21;37(2):268-74.
37 Sodium channel blockers: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):279-90.
38 Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as use-dependent sodium channel blockers for the treatment of stroke. J Med Chem. 2002 Aug 15;45(17):3755-64.
39 Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a ... J Med Chem. 2000 Sep 7;43(18):3372-6.