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) 44 Target ID: CHEMBL2093867 Sources: http://www.bioscreening.net/glossary/gossypol/	Inhibitor 8504
Calcineurin 3 Target ID: Calcineurin Sources: https://www.ncbi.nlm.nih.gov/pubmed/17141216	Inhibitor 8504	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 8504	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 8504	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 8504	3.4 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pregnancy 65 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12020773	Preventing	Phase III 665	Unknown Approved Use Unknown
Adrenocortical carcinoma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7544429	Primary	Phase II 1147	Unknown Approved Use Unknown
Glioblastoma multiforme 30 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24968413	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
315 ng/mL EXPERIMENT https://link.springer.com/article/10.1023/A:1010686204736	30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
278.8 ng/mL EXPERIMENT https://link.springer.com/article/10.1023/A:1010686204736	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.61 μg/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1986.108?sid=nlm%3Apubmed	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.66 μg/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1986.108?sid=nlm%3Apubmed	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: ISOSORBIDE	ISOSORBIDE	GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
15.8 mg × h/L EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1986.108?sid=nlm%3Apubmed	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.53 μg × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1986.108?sid=nlm%3Apubmed	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: ISOSORBIDE	ISOSORBIDE	GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
286 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1986.108?sid=nlm%3Apubmed	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.33 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1986.108?sid=nlm%3Apubmed	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: ISOSORBIDE	ISOSORBIDE	GOSSYPOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Towards a systematic analysis of human short-chain dehydrogenases/reductases (SDR): Ligand identification and structure-activity relationships.	2015-06-05	25526675
Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells.	2011-03-24	21332213
Mirabamides E-H, HIV-inhibitory depsipeptides from the sponge Stelletta clavosa.	2011-02-25	21280591
The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma.	2010-07	20587533
Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression.	2010-02-02	20133848
Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells.	2009-09	19825521
-(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro.	2008-05-12	18840529
A fluorescence-based coupling reaction for monitoring the activity of recombinant human NAD synthetase.	2005-10	16305310
Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL.	2005-07	16020667
A combined regimen of gossypol plus methyltestosterone and ethinylestradiol as a contraceptive induces germ cell apoptosis and expression of its related genes in rats.	2004-10	15451339
Sertoli cell junctional proteins as early targets for different classes of reproductive toxicants.	2004-05	15082077
Effect of gossypol in association with chromium protoporphyrin on heme metabolic enzymes.	2004-02	15027808
Type of cottonseed and level of gossypol in diets of lactating dairy cows: plasma gossypol, health, and reproductive performance.	2003-03	12703626
Gossypol and gossypolone enantiomers in tissues of rainbow trout fed low and high levels of dietary cottonseed meal.	2002-05-08	11982441
Low dose gossypol for male contraception.	2000-12	11202417
Gossypol as a male antifertility agent--why studies should have been continued.	1998-02	9639145
Synthesis and anti-HIV activity of 1,1'-dideoxygossypol and related compounds.	1995-06-23	7608907
Comparative in vitro study of contraceptive agents with anti-HIV activity: gramicidin, nonoxynol-9, and gossypol.	1994-02	7511493
Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.	1993-12	7508328
Anti-HIV-1 activity and cellular pharmacology of various analogs of gossypol.	1993-07-20	8347147
Inhibition of human immunodeficiency virus type I replication by derivatives of gossypol.	1991-12	1805194
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.	1991-01-01	1710653
Selective inhibition of human immunodeficiency virus type 1 replication by the (-) but not the (+) enantiomer of gossypol.	1989-12	2619282
Inactivation of human immunodeficiency virus in vitro by gossypol.	1989-06	2473865
Monkey lactate dehydrogenase-C4 as a model for the interaction of enzymes with gossypol.	1986-06	3769483
Screening for new compounds with antiherpes activity.	1984-10	6517562

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

Preferred Name

English

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

R-(-)-GOSSYPOL

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

230206