GOSSYPOL, (R)-

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H30O8
Molecular Weight	518.5544
Optical Activity	NONE
Additional Stereochemistry	Yes
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0
Stereo Comments	AXIAL, R

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C1=C(O)C(O)=C(C=O)C2=C(O)C(=C(C)C=C12)C3=C(O)C4=C(C=C3C)C(C(C)C)=C(O)C(O)=C4C=O

InChI

InChIKey=QBKSWRVVCFFDOT-UHFFFAOYSA-N

InChI=1S/C30H30O8/c1-11(2)19-15-7-13(5)21(27(35)23(15)17(9-31)25(33)29(19)37)22-14(6)8-16-20(12(3)4)30(38)26(34)18(10-32)24(16)28(22)36/h7-12,33-38H,1-6H3

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/npp/gossypol.html
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/24073600 | http://www.webmd.com/vitamins-supplements/ingredientmono-106-gossypol.aspx?activeingredientid=106&activeingredientname=gossypol

Gossypol is a substance that is found in the cotton plant. It is removed from the seeds and used for medicine. Gossypol is effective as a nonhormonal male contraceptive; however, it has been documented to have irreversible effects on male fertility. Gossypol is reported to exhibit antioxidant, anticancer, antivirus, antiparasitic, and antimicrobial properties and lower plasma cholesterol. Nausea, emesis, anorexia, diarrhea, altered taste sensation, small intestine obstruction, and fatigue have been recorded in clinical trials as adverse reactions. Large amounts of gossypol can decrease potassium levels in the body. Low potassium levels can increase the side effects of digoxin.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Protein kinase C (PKC) 43 Target ID: CHEMBL2093867 Sources: http://www.bioscreening.net/glossary/gossypol/	Inhibitor 8146
Target ID: Calcineurin Sources: https://www.ncbi.nlm.nih.gov/pubmed/17141216	Inhibitor 8146	14.2 µM [IC50]
Inositol-trisphosphate 3-kinase A 1 Target ID: P23677 Gene ID: 3706.0 Gene Symbol: ITPKA Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15659385	Inhibitor 8146	115.0 nM [IC50]
Inositol-trisphosphate 3-kinase B 1 Target ID: P27987 Gene ID: 3707.0 Gene Symbol: ITPKB Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15659385	Inhibitor 8146	340.0 nM [IC50]
Inositol polyphosphate multikinase 1 Target ID: Q8NFU5 Gene ID: 253430.0 Gene Symbol: IPMK Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15659385	Inhibitor 8146	3.4 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pregnancy 62 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12020773	Preventing	Phase III 651	Unknown Approved Use Unknown
Adrenocortical carcinoma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7544429	Primary	Phase II 1133	Unknown Approved Use Unknown
Glioblastoma multiforme 29 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24968413	Primary	Phase II 1133	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Monkey lactate dehydrogenase-C4 as a model for the interaction of enzymes with gossypol.	1986 Jun	3769483
Selective inhibition of human immunodeficiency virus type 1 replication by the (-) but not the (+) enantiomer of gossypol.	1989 Dec	2619282
Inactivation of human immunodeficiency virus in vitro by gossypol.	1989 Jun	2473865
Inhibition of human immunodeficiency virus type I replication by derivatives of gossypol.	1991 Dec	1805194
Gossypol as a male antifertility agent--why studies should have been continued.	1998 Feb	9639145
A combined regimen of gossypol plus methyltestosterone and ethinylestradiol as a contraceptive induces germ cell apoptosis and expression of its related genes in rats.	2004 Oct	15451339
Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL.	2005 Jul	16020667
The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma.	2010 Jul	20587533

Patents

Sample Use Guides

In Vivo Use Guide

15 mg per day for 12 weeks or, if needed, for 16 weeks to reach spermatogenesis suppression.

Route of Administration: Oral

In Vitro Use Guide

In the testing of the possibility of the inactivation of HIV, it was found that a concentration of 100uM of gossypol completely inactivates cell-free preparations of HIV. Following exposure of cell-free incubates of HIV to 100 uM gossypol, ultracentrifugation and inoculation of the washed pellet onto H9 cells, there is no evidence of elevated reverse transcriptase activity over 21 days. Treatment with lower concentrations of gossypol reduces the peak and lengthens the time to maximal reverse transcriptase activity compared with control cultures.

Name

Type

Language

GOSSYPOL, (R)-

Common Name

English

(R)-2,2'-BIS(8-FORMYL-1,6,7-TRIHYDROXY-5-ISOPROPYL-3-METHYLNAPHTHALENE)

Common Name

English

(R)-GOSSYPOL

Common Name

English

NSC-726190

Code

English

GOSSYPOL R-FORM [MI]

Common Name

English

GOSSYPOL, R-

Common Name

English

(-)-GOSSYPOL

Common Name

English

R-(-)-GOSSYPOL

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

230206