Details of the Drug

General Information of Drug (ID: DMJWD62)

Drug Name

phorbol 12-myristate 13-acetate

Synonyms

TPA; 12-O-tetradecanoylphorbol-13-acetate; tetradecanoyl-beta-phorbol acetate

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Phase 2	[1]
Hodgkin lymphoma	2B30	Phase 2	[1]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

616.8

Topological Polar Surface Area (xlogp)

6.5

Rotatable Bond Count (rotbonds)

17

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C36H56O8
IUPAC Name: [(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate
Canonical SMILES: CCCCCCCCCCCCCC(=O)O[C@@H]1[C@H]([C@]2([C@@H](C=C(C[C@]3([C@H]2C=C(C3=O)C)O)CO)[C@H]4[C@@]1(C4(C)C)OC(=O)C)O)C
InChI: InChI=1S/C36H56O8/c1-7-8-9-10-11-12-13-14-15-16-17-18-29(39)43-32-24(3)35(42)27(30-33(5,6)36(30,32)44-25(4)38)20-26(22-37)21-34(41)28(35)19-23(2)31(34)40/h19-20,24,27-28,30,32,37,41-42H,7-18,21-22H2,1-6H3/t24-,27+,28-,30-,32-,34-,35-,36-/m1/s1
InChIKey: PHEDXBVPIONUQT-RGYGYFBISA-N

Cross-matching ID

PubChem CID: 27924
ChEBI ID: CHEBI:37537
CAS Number: 16561-29-8
TTD ID: D09DHT

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Calcium-activated potassium channel KCa4.1 (KCNT1)	TTGJFK1	KCNT1_HUMAN	Activator	[2]
Calcium-activated potassium channel KCa4.2 (KCNT2)	TTLU5FO	KCNT2_HUMAN	Inhibitor (gating inhibitor)	[2]
Inward rectifier potassium channel Kir3.4 (KCNJ5)	TTEO25X	KCNJ5_HUMAN	Inhibitor (gating inhibitor)	[3]
Transient receptor potential cation channel V4 (TRPV4)	TTKP2SU	TRPV4_HUMAN	Activator	[4]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	Opposite regulation of Slick and Slack K+ channels by neuromodulators. J Neurosci. 2006 May 10;26(19):5059-68.
3	Molecular basis for the inhibition of G protein-coupled inward rectifier K(+) channels by protein kinase C. Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):1087-92.
4	Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem. 2002 Apr 19;277(16):13569-77.
5	For K+ channels, Na+ is the new Ca2+. Trends Neurosci. 2005 Aug;28(8):422-8.
6	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: 385).
7	Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
8	Impaired pressure sensation in mice lacking TRPV4. J Biol Chem. 2003 Jun 20;278(25):22664-8.
9	N-4-methansulfonamidobenzyl-N'-2-substituted-4-tert-butyl-benzyl thioureas as potent vanilloid receptor antagonistic ligands. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1693-6.
10	Chain-branched acyclic phenethylthiocarbamates as vanilloid receptor antagonists. Bioorg Med Chem Lett. 2003 May 5;13(9):1549-52.
11	Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural requirement for VR1 antagonistic effects. Bioorg Med Chem Lett. 2003 Dec 15;13(24):4389-93.
12	Bisandrographolide from Andrographis paniculata activates TRPV4 channels. J Biol Chem. 2006 Oct 6;281(40):29897-904.
13	N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther. 2008 Aug;326(2):432-42.
14	An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med. 2012 Nov 7;4(159):159ra148.
15	Identification and characterization of novel TRPV4 modulators. Biochem Biophys Res Commun. 2009 Nov 20;389(3):490-4.
16	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: 386).
17	PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science. 1998 Nov 6;282(5391):1141-4.