Gossypol | CAS#303-45-7 | Bcl antagonist

MedKoo Cat#: 201430 | Name: Gossypol

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Gossypol is an orally-active polyphenolic aldehyde with potential antineoplastic activity. Derived primarily from unrefined cottonseed oil, gossypol induces cell cycle arrest at the G0/G1 phase, thereby inhibiting DNA replication and inducing apoptosis. This agent also inhibits cell-signaling enzymes, resulting in inhibition of cell growth, and may act as a male contraceptive.

Chemical Structure

Gossypol

CAS#303-45-7 (free)

Theoretical Analysis

MedKoo Cat#: 201430

Name: Gossypol

CAS#: 303-45-7 (free)

Chemical Formula: C30H30O8

Exact Mass: 518.1941

Molecular Weight: 518.55

Elemental Analysis: C, 69.49; H, 5.83; O, 24.68

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to Ship
50mg	USD 150.00	Ready to Ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 950.00	Ready to ship
1g	USD 1,650.00	Ready to ship
2g	USD 2,950.00	Ready to ship

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Related CAS #

12542-36-8 (acetic acid) 303-45-7 (free) 812542-36-8 (R-isomer acetic acid)

Synonym

Cottonseed Meal Toxin; Gossypol; BL 193; BL-193; BL193; NSC 56817; NSC 624336; Pogosin;

IUPAC/Chemical Name

1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalene]-8,8'-dicarbaldehyde

InChi Key

QBKSWRVVCFFDOT-UHFFFAOYSA-N

InChi Code

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

SMILES Code

O=CC1=C(O)C(O)=C(C(C)C)C2=CC(C)=C(C3=C(C)C=C4C(C(C)C)=C(O)C(O)=C(C=O)C4=C3O)C(O)=C12

Appearance

Solid powder

Purity

>98%

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Gossypol is a polyphenol derived from the cotton plant (genus Gossypium, family Malvaceae). Gossypol is a polyphenolic aldehyde that permeates cells and acts as an inhibitor for several dehydrogenase enzymes. It is a yellow pigment. Among other things, it has been tested as a male oral contraceptive in China. In addition to its contraceptive properties, gossypol has also long been known to possess antimalarial properties. Other researchers are investigating the anticancer properties of gossypol. Oncology testing (from: http://en.wikipedia.org/wiki/Gossypol) Gossypol is also under investigation as a possible chemotherapy drug especially in its R- state. It is currently believed that gossypol in itself will not kill cancerous cells, however it changes the chemistry within the cancer cell and makes it more susceptible to traditional chemotherapy drugs. Phased trials have been done on resistant prostate and lung cancer. Few results have been published to date so no conclusions can be drawn. Contraceptive use (from: http://en.wikipedia.org/wiki/Gossypol) A 1929 investigation in Jiangxi showed correlation between low fertility in males and use of crude cottonseed oil for cooking. The compound causing the contraceptive effect was determined to be gossypol. In the 1970s, the Chinese government began researching the use of gossypol as a contraceptive. Their studies involved over 10,000 subjects, and continued for over a decade. They concluded that gossypol provided reliable contraception, could be taken orally as a tablet, and did not upset men's balance of hormones. However, gossypol also had serious flaws. The studies also discovered an abnormally high rate of hypokalemia among subjects. Hypokalemia Â— low blood potassium levels Â— causes symptoms of fatigue, muscle weakness, and at its most extreme, paralysis. In addition, about 7% of subjects reported effects on their digestive system, and about 12% increased fatigue. Most subjects recovered after stopping treatment and taking potassium supplements. A later study showed that taking potassium supplements during gossypol treatment did not prevent hypokalemia in primates. In the mid-1990s, the Brazilian pharmaceutical company Hebron announced plans to market a low-dose gossypol pill called Nofertil, but the pill never came to market. Its release was indefinitely postponed due to unacceptably high rates of permanent infertility. Between five and twenty-five percent of the men remained azoospermic up to a year after stopping treatment. The longer the men had taken the drug and the higher their overall dosage, the more likely the men were to have lowered fertility or to become completely infertile. Researchers have suggested that gossypol might make a good non-invasive alternative to surgical vasectomy. In 1986, the Chinese stopped research because of these side effects. In 1998, the World Health Organization's Research Group on Methods for the Regulation of Male Fertility recommended that research should be abandoned. In addition to the other side effects, the WHO researchers were concerned about gossypol's toxicity: the toxic dose in primates is less than 10 times the contraceptive dose. This report effectively ended further studies of gossypol as a temporary contraceptive, but research into using it as an alternative to vasectomy continues in Austria, Brazil, Chile, China, the Dominican Republic, and Nigeria. Current developer:

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T08K05

QC Data

View QC data: current batch, Lot#A8T08K05

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Gossypol, a natural product isolated from cottonseeds and roots, binds to Bcl-xL protein and Bcl-2 protein with Kis of 0.5-0.6 μM and 0.2-0.3 mM, respectively.

In vitro activity:

The in vitro effects of (-)-gossypol on HNSCC cell lines as well as on fibroblast and keratinocyte cultures were investigated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell survival assays and assessed the results with respect to Bcl-2 family protein expression. It was observed that dose-dependent growth inhibition of 10 HNSCC cell lines at biologically achievable doses (2.5-10 micromol/L). (-)-Gossypol doses required to inhibit the growth of human fibroblast cell lines by 50% were 2- to 10-fold higher than for HNSCC cell lines. To inhibit human oral keratinocyte growth by 50%, (-)-gossypol concentrations were 2-to 3-fold higher than for HNSCC cell lines. Reference: Clin Cancer Res. 2004 Nov 15;10(22):7757-63. http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15570010

In vivo activity:

To evaluate the effects of gossypol on bone formation, histological analysis was first performed with ovariectomy-induced osteoporosis mice. As shown in Figure 1(a), gossypol-injected mice showed relieved osteoporosis as characterized by a remarkable increase in the trabeculae of epiphyseal (red arrows) and metaphyseal regions (black arrows) when compared with the control mice. The increased thickness of cortical bone was also observed in the metaphyseal region in the gossypol-treated group (data not shown). Furthermore, several serum chemicals were analyzed with Elisa methods in both groups. It was shown that the serum osteocalcin levels in gossypol-injected mice were significantly higher than the control counterpart (Figure 1(b)). Furthermore, the serum OPG levels in the experimental mice were increased to 2-fold of the control group (Figure 1(c)) and the serum RANKL levels were decreased by approximate 50% (Figure 1(d)), causing the ratio of RANKL to OPG to drop to 25% in the gossypol-injected mice in comparison with the control group (Figure 1(e)). Reference: Biomed Res Int. 2018 Dec 13;2018:3635485. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30643801/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	192.85
	Ethanol	8.0	15.43

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 518.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Oliver CL, Bauer JA, Wolter KG, Ubell ML, Narayan A, O'Connell KM, Fisher SG, Wang S, Wu X, Ji M, Carey TE, Bradford CR. In vitro effects of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res. 2004 Nov 15;10(22):7757-63. doi: 10.1158/1078-0432.CCR-04-0551. Erratum in: Clin Cancer Res. 2005 Aug 1;11(15):5659. PMID: 15570010. 2. Lim W, Ham J, Park S, Bae H, You S, Song G. Gossypol Induces Disruption of Spermatogenesis and Steroidogenesis in Male Mice. J Agric Food Chem. 2019 Feb 20;67(7):2075-2085. doi: 10.1021/acs.jafc.8b06946. Epub 2019 Feb 8. PMID: 30678458.

In vivo protocol:

1. Liang J, Chen C, Liu H, Liu X, Li Z, Hu J, Zhao H. Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis. Biomed Res Int. 2018 Dec 13;2018:3635485. doi: 10.1155/2018/3635485. PMID: 30643801; PMCID: PMC6311247. 2. Lim W, Ham J, Park S, Bae H, You S, Song G. Gossypol Induces Disruption of Spermatogenesis and Steroidogenesis in Male Mice. J Agric Food Chem. 2019 Feb 20;67(7):2075-2085. doi: 10.1021/acs.jafc.8b06946. Epub 2019 Feb 8. PMID: 30678458.

1: Ye W, Chang HL, Wang LS, Huang YW, Shu S, Sugimoto Y, Dowd MK, Wan PJ, Lin YC. Induction of apoptosis by (-)-gossypol-enriched cottonseed oil in human breast cancer cells. Int J Mol Med. 2010 Jul;26(1):113-9. PubMed PMID: 20514430. 2: Zhang XQ, Huang XF, Mu SJ, An QX, Xia AJ, Chen R, Wu DC. Inhibition of proliferation of prostate cancer cell line, PC-3, in vitro and in vivo using (-)-gossypol. Asian J Androl. 2010 May;12(3):390-9. Epub 2010 Jan 18. PubMed PMID: 20081872. 3: Xu P, Ye W, Jen R, Lin SH, Kuo CT, Lin YC. Mitogenic activity of zeranol in human breast cancer cells is enhanced by leptin and suppressed by gossypol. Anticancer Res. 2009 Nov;29(11):4621-8. PubMed PMID: 20032412. 4: Wang X, Howell CP, Chen F, Yin J, Jiang Y. Gossypol--a polyphenolic compound from cotton plant. Adv Food Nutr Res. 2009;58:215-63. Review. PubMed PMID: 19878861. 5: Zerp SF, Stoter R, Kuipers G, Yang D, Lippman ME, van Blitterswijk WJ, Bartelink H, Rooswinkel R, Lafleur V, Verheij M. AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis. Radiat Oncol. 2009 Oct 23;4:47. PubMed PMID: 19852810; PubMed Central PMCID: PMC2771029. 6: Wang J, Zhou JY, Zhang L, Wu GS. Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells. Cell Cycle. 2009 Oct 1;8(19):3191-8. Epub 2009 Oct 7. PubMed PMID: 19755862. 7: Hu ZY, Sun J, Zhu XF, Yang D, Zeng YX. ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway. J Transl Med. 2009 Aug 23;7:74. PubMed PMID: 19698176; PubMed Central PMCID: PMC2742515. 8: El-Sharaky AS, Wahby MM, Bader El-Dein MM, Fawzy RA, El-Shahawy IN. Mutual anti-oxidative effect of gossypol acetic acid and gossypol-iron complex on hepatic lipid peroxidation in male rats. Food Chem Toxicol. 2009 Nov;47(11):2735-41. Epub 2009 Aug 6. PubMed PMID: 19665044. 9: Zhang L, Jiang H, Cao X, Zhao H, Wang F, Cui Y, Jiang B. Chiral gossypol derivatives: evaluation of their anticancer activity and molecular modeling. Eur J Med Chem. 2009 Oct;44(10):3961-72. Epub 2009 Apr 22. PubMed PMID: 19447525. 10: Stipanovic RD, Puckhaber LS, Liu J, Bell AA. Total and percent atropisomers of gossypol and gossypol-6-methyl ether in seeds from pima cottons and accessions of Gossypium barbadense L. J Agric Food Chem. 2009 Jan 28;57(2):566-71. PubMed PMID: 19113939. 11: Zhai G, Wu J, Zhao X, Yu B, Li H, Lu Y, Ye W, Lin YC, Lee RJ. A liposomal delivery vehicle for the anticancer agent gossypol. Anticancer Res. 2008 Sep-Oct;28(5A):2801-5. PubMed PMID: 19035313. 12: Etxebarria A, Landeta O, Antonsson B, BasaÃ±ez G. Regulation of antiapoptotic MCL-1 function by gossypol: mechanistic insights from in vitro reconstituted systems. Biochem Pharmacol. 2008 Dec 1;76(11):1563-76. Epub 2008 Aug 12. PubMed PMID: 18762177. 13: Marzo I, Naval J. Bcl-2 family members as molecular targets in cancer therapy. Biochem Pharmacol. 2008 Oct 15;76(8):939-46. Epub 2008 Jun 28. PubMed PMID: 18638457. 14: Wang L, Sloper DT, Addo SN, Tian D, Slaton JW, Xing C. WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth. Cancer Res. 2008 Jun 1;68(11):4377-83. PubMed PMID: 18519699; PubMed Central PMCID: PMC2410026. 15: Wang X, Beckham TH, Morris JC, Chen F, Gangemi JD. Bioactivities of gossypol, 6-methoxygossypol, and 6,6'-dimethoxygossypol. J Agric Food Chem. 2008 Jun 25;56(12):4393-8. Epub 2008 Jun 3. PubMed PMID: 18517219. 16: Ye W, Chang HL, Wang LS, Huang YW, Shu S, Dowd MK, Wan PJ, Sugimoto Y, Lin YC. Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil. Anticancer Res. 2007 Jan-Feb;27(1A):107-16. PubMed PMID: 17352222. 17: Zhang M, Liu H, Tian Z, Huang J, Remo M, Li QQ. Differential growth inhibition and induction of apoptosis by gossypol between HCT116 and HCT116/Bax(-/-) colorectal cancer cells. Clin Exp Pharmacol Physiol. 2007 Mar;34(3):230-7. PubMed PMID: 17250644. 18: Yeow WS, Baras A, Chua A, Nguyen DM, Sehgal SS, Schrump DS, Nguyen DM. Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Thorac Cardiovasc Surg. 2006 Dec;132(6):1356-62. Epub 2006 Oct 30. PubMed PMID: 17140955. 19: Konac E, Ekmekci A, Yurtcu E, Ergun MA. An in vitro study of cytotoxic effects of gossypol on human epidermoid larynx carcinoma cell line (HEp-2). Exp Oncol. 2005 Mar;27(1):81-3. PubMed PMID: 15812364. 20: Xu L, Yang D, Wang S, Tang W, Liu M, Davis M, Chen J, Rae JM, Lawrence T, Lippman ME. (-)-Gossypol enhances response to radiation therapy and results in tumor regression of human prostate cancer. Mol Cancer Ther. 2005 Feb;4(2):197-205. PubMed PMID: 15713891.