Natural Product (NP) Details

General Information of the NP (ID: NP1197)
Name
12-O-tetradecanoyl phorbol-13-acetate
Synonyms
TPA; 12-O-tetradecanoylphorbol-13-acetate; tetradecanoyl-beta-phorbol acetate
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Species Origin Homo sapiens ...     Click to Show/Hide
Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Disease Acute myeloid leukemia [ICD-11: 2A60] Phase 2 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.243
 
MDCK Permeability
 -4.773
 
PAMPA
 +
 
HIA
 +++
 
Distribution
VDss
 0.642
 
PPB
 96.7%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 +++
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 ++
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 +++
CYP3A4 substrate
 -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 ++
 
Excretion
CLplasma
 3.004
 
T1/2
 1.557
Toxicity
DILI
 - -
 
Rat Oral Acute Toxicity
 +
 
FDAMDD
 +
 
Respiratory
 ++
 
Human Hepatotoxicity
 +
 
Ototoxicity
 ++
 
Drug-induced Nephrotoxicity
 - -
 
Drug-induced Neurotoxicity
 - -
 
Hematotoxicity
 - -
 
Genotoxicity
 - - -
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C36H56O8
PubChem CID
27924
Canonical SMILES
CCCCCCCCCCCCCC(=O)OC1C(C2(C(C=C(CC3(C2C=C(C3=O)C)O)CO)C4C1(C4(C)C)OC(=O)C)O)C
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
CAS Number
CAS 16561-29-8
TTD Drug ID
D09DHT
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Ionizing radiation      Renal Insufficiency     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction ROS accumulation
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Ionizing radiation enhances PMA-induced megakaryocytic differentiation at a relatively late phase, and that the late-phase accelerated differentiation depends on the persistence of the intracellular ROS level.
Target and Pathway
Target(s) Potassium channel J5 Kir3.4 (KCNJ5)  Molecule Info  [3]
Potassium channel T1 KCa4.1 (KCNT1)  Molecule Info  [4]
Potassium channel T2 KCa4.2 (KCNT2)  Molecule Info  [4]
Transient receptor cation channel V4 (TRPV4)  Molecule Info  [5]
KEGG Pathway Circadian entrainment Click to Show/Hide
2 Retrograde endocannabinoid signaling
3 Serotonergic synapse
4 Dopaminergic synapse
5 Estrogen signaling pathway
6 Oxytocin signaling pathway
7 Morphine addiction
8 Inflammatory mediator regulation of TRP channels
Panther Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway Click to Show/Hide
2 Muscarinic acetylcholine receptor 2 and 4 signaling pathway
Pathwhiz Pathway Muscle/Heart Contraction Click to Show/Hide
Reactome Activation of G protein gated Potassium channels Click to Show/Hide
2 Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
3 TRP channels
WikiPathways Calcium Regulation in the Cardiac Cell Click to Show/Hide
2 Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
3 Notch Signaling Pathway
4 Potassium Channels
References
Reference 1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Reference 2 Megakaryocytic differentiation in human chronic myelogenous leukemia K562 cells induced by ionizing radiation in combination with phorbol 12-myristate 13-acetate. J Radiat Res. 2013 May;54(3):438-46.
Reference 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.
Reference 4 Opposite regulation of Slick and Slack K+ channels by neuromodulators. J Neurosci. 2006 May 10;26(19):5059-68.
Reference 5 Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem. 2002 Apr 19;277(16):13569-77.
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