Thalidomide
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MedKoo CAT#: 100840

CAS#: 50-35-1

Description: Thalidomide is a synthetic derivative of glutamic acid (alpha-phthalimido-glutarimide) with teratogenic, immunomodulatory, anti-inflammatory and anti-angiogenic properties. Thalidomide acts primarily by inhibiting both the production of tumor necrosis factor alpha (TNF-alpha) in stimulated peripheral monocytes and the activities of interleukins and interferons. This agent also inhibits polymorphonuclear chemotaxis and monocyte phagocytosis. In addition, thalidomide inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), thereby inhibiting angiogenesis.


Chemical Structure

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Thalidomide
CAS# 50-35-1

Theoretical Analysis

MedKoo Cat#: 100840
Name: Thalidomide
CAS#: 50-35-1
Chemical Formula: C13H10N2O4
Exact Mass: 258.06
Molecular Weight: 258.230
Elemental Analysis: C, 60.47; H, 3.90; N, 10.85; O, 24.78

Price and Availability

Size Price Availability Quantity
1g USD 90 Ready to ship
2g USD 150 Ready to ship
5g USD 250 Ready to ship
10g USD 450 Ready to ship
20g USD 750 Ready to ship
50g USD 1450 Ready to ship
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Synonym: alphaphthalimidoglutarimide. Nphthaloylglutamimide; Nphthalylglutamic acid imide. US brand names: Synovir; Thalomid. Foreign brand names: Contergan; Distaval; Kevadon; Neurosedyn; Pantosediv; Sedoval K17; Softenon Talimol; Abbreviation: THAL.

IUPAC/Chemical Name: 2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

InChi Key: UEJJHQNACJXSKW-UHFFFAOYSA-N

InChi Code: InChI=1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)

SMILES Code: O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

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: >2 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: Chemical structures: Chemical structures of Pomalidomide; Thalidomide and Lenalidomide are very similar:   Thalidomide is an off-white to white, odorless, crystalline powder that is soluble at 25°C in dimethyl sulfoxide and sparingly soluble in water and ethanol. The glutarimide moiety contains a single asymmetric center and, therefore, may exist in either of two optically active forms designated S-(-) or R-(+). THALOMID® (thalidomide) is an equal mixture of the S-(-) and R-(+) forms and, therefore, has a net optical rotation of zero. THALOMID® (thalidomide) is available in 50 mg, 100 mg, 150 mg and 200 mg capsules for oral administration. Active ingredient: thalidomide. Inactive ingredients: pregelatinized starch and magnesium stearate. The 50 mg capsule shell contains gelatin, titanium dioxide, and black ink. The 100 mg capsule shell contains black iron oxide, yellow iron oxide, titanium dioxide, gelatin, and black ink. The 150 mg capsule shell contains FD&C blue #2, black iron oxide, yellow iron oxide, titanium dioxide, gelatin, and black and white ink. The 200 mg capsule shell contains FD&C blue #2, titanium dioxide, gelatin, and white ink.   According to http://en.wikipedia.org/wiki/Thalidomide, Thalidomide was introduced as a sedative drug in the late 1950s. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used primarily, combined with dexamethasone, to treat multiple myeloma. The drug is a potent teratogen in zebrafish, chickens, rabbits and primates including humans: severe birth defects may result if the drug is taken during pregnancy. Thalidomide was sold in a number of countries across the world from 1957 until 1961 when it was withdrawn from the market after being found to be a cause of birth defects in what has been called "one of the biggest medical tragedies of modern times".[4] It is not known exactly how many worldwide victims of the drug there have been, although estimates range from 10,000 to 20,000. Since then thalidomide has been found to be a valuable treatment for a number of medical conditions and it is being prescribed again in a number of countries, although its use remains controversial.  The thalidomide tragedy led to much stricter testing being required for drugs and pesticides before they can be licensed.   Thalidomide was developed by German pharmaceutical company Grünenthal in Stolberg (Rhineland) near Aachen, although this claim has recently been challenged. A report published by Martin W. Johnson, director of the Thalidomide Trust in the United Kingdom, mentioned evidence found by Argentinian author Carlos De Napoli that suggested the drug had been developed as an antidote to nerve gases such as Sarin in Germany in 1944, ten years before Grünenthal secured a patent in 1954. De Napoli suggested elsewhere that thalidomide may have been first synthesised by British scientists at the University of Nottingham in 1949. Thalidomide, launched by Grünenthal on 1st October 1957,  was found to act as an effective tranquiliser and painkiller and was proclaimed a "wonder drug" for insomnia, coughs, colds and headaches. It was also found to be an effective antiemetic which had an inhibitory effect on morning sickness, and so thousands of pregnant women took the drug to relieve their symptoms. At the time of the drug's development it was not thought likely that any drug could pass from the mother across the placental barrier and harm the developing fetus.     In 1964 Jacob Sheskin, Professor at the Hebrew University of Jerusalem at Hadassah University Hospital (he was also the chief staff and manager of Hansen Leper Hospital in Jerusalem), administered thalidomide to a critically ill patient with erythema nodosum leprosum (ENL), a painful complication of leprosy, in an attempt to relieve his pain in spite of the ban. The patient slept for hours, and was able to get out of bed without aid upon awakening. The result was followed by more favorable experiences and then by a clinical trial.[24] He found that patients with erythema nodosum leprosum, a painful skin condition, experienced relief of their pain by taking thalidomide. Further work conducted in 1991 by Dr. Gilla Kaplan at Rockefeller University in New York City showed that thalidomide worked in leprosy by inhibiting tumor necrosis factor alpha and believed it would be an effective treatment for AIDS. Kaplan partnered with Celgene Corporation to further develop the potential for thalidomide in AIDS and tuberculosis. However, clinical trials for AIDS proved disappointing. In 1964 Jacob Sheskin, Professor at the Hebrew University of Jerusalem at Hadassah University Hospital (he was also the chief staff and manager of Hansen Leper Hospital in Jerusalem), administered thalidomide to a critically ill patient with erythema nodosum leprosum (ENL), a painful complication of leprosy, in an attempt to relieve his pain in spite of the ban. The patient slept for hours, and was able to get out of bed without aid upon awakening. The result was followed by more favorable experiences and then by a clinical trial.[24] He found that patients with erythema nodosum leprosum, a painful skin condition, experienced relief of their pain by taking thalidomide. Further work conducted in 1991 by Dr. Gilla Kaplan at Rockefeller University in New York City showed that thalidomide worked in leprosy by inhibiting tumor necrosis factor alpha and believed it would be an effective treatment for AIDS. Kaplan partnered with Celgene Corporation to further develop the potential for thalidomide in AIDS and tuberculosis. However, clinical trials for AIDS proved disappointing. On July 16, 1998, the FDA approved the use of thalidomide for the treatment of lesions associated with Erythema Nodosum Leprosum (ENL). Because of thalidomideÂ’s potential for causing birth defects, the distribution of the drug was permitted only under tightly controlled conditions. The FDA required that Celgene Corporation, which planned to market thalidomide under the brand name Thalomid, establish a System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) oversight program. The conditions required under the program include; limiting prescription and dispensing rights only to authorized prescribers and pharmacies, keeping a registry of all patients prescribed thalidomide, providing extensive patient education about the risks associated with the drug and providing periodic pregnancy tests for women who are prescribed it.On May 26, 2006, the U.S. Food and Drug Administration granted accelerated approval for thalidomide (Thalomid, Celgene Corporation) in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma (MM) patients.The FDA approval came seven years after the first reports of efficacy in the medical literature and Celgene took advantage of "off-label" marketing opportunities to promote the drug in advance of its FDA approval for the myeloma indication. Thalomid, as the drug is commercially known, sold over $300 million per year, while only approved for leprosy. From: http://en.wikipedia.org/wiki/Thalidomide    

Biological target: Thalidomide-5-OH is the Thalidomide-based cereblon ligand used in the recruitment of CRBN protein.
In vitro activity: Thalidomide upregulated five genes (AICDA, BMP, LEFTY1, LEFTY2, and TBX3) and downregulated one gene (ACTC1) (Table 1, Fig. 1B and C). The ratio of regulated genes, genes without change, and downregulated genes (5, 55, 1) was significantly different from the hypothetical ratio without change (0, 61, 0) (Fig. 1D, Fisher's exact test, P = 0.027). However, the ratio (5, 55, 1) was not significantly different from the hypothetical ratio with equal up- and downregulation (3, 55, 3) (Fig. 1D, Fisher's exact test, P = 0.581). These results suggest that although thalidomide affects undifferentiated hiPSCs, it might not facilitate or inhibit the undifferentiated state. Notably, three transforming growth factor β (TGF-β) genes (BMP2, LEFTY1, and LEFTY2), which are related to mesoderm differentiation, including limb formation, were upregulated (Fig. 1B). Reference: Biochem Biophys Rep. 2021 Mar 13;26:100978. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973312/
In vivo activity: The CRBN protein is involved in thalidomide-induced degradation of EGFL6. Overexpression of EGFL6 induced the development of abnormal subintestinal vein vessels in a zebrafish model, a process that was impaired by knocking down PAX6 or treatment with thalidomide. These findings established that thalidomide regulates EGFL6 expression through proteasome degradation to inhibit the EGFL6/PAX6 axis-driven angiogenesis in SBVM. Reference: Cell Mol Life Sci. 2020; 77(24): 5207–5221. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671996/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 33.0 127.79
DMSO:PBS (pH 7.2) (1:8) 0.1 0.43
DMF 12.0 46.47

Preparing Stock Solutions

The following data is based on the product molecular weight 258.23 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.

Recalculate based on batch purity %
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: 1. Shimizu M, Tachikawa S, Saitoh N, Nakazono K, Yu-Jung L, Suga M, Ohnuma K. Thalidomide affects limb formation and multiple myeloma related genes in human induced pluripotent stem cells and their mesoderm differentiation. Biochem Biophys Rep. 2021 Mar 13;26:100978. doi: 10.1016/j.bbrep.2021.100978. PMID: 33763605; PMCID: PMC7973312. 2. Liao H, Li Y, Zhang X, Zhao X, Zheng D, Shen D, Li R. Protective Effects of Thalidomide on High-Glucose-Induced Podocyte Injury through In Vitro Modulation of Macrophage M1/M2 Differentiation. J Immunol Res. 2020 Aug 27;2020:8263598. doi: 10.1155/2020/8263598. PMID: 32908940; PMCID: PMC7474395. 3. Tang CT, Zhang QW, Wu S, Tang MY, Liang Q, Lin XL, Gao YJ, Ge ZZ. Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation. Cell Mol Life Sci. 2020 Dec;77(24):5207-5221. doi: 10.1007/s00018-020-03465-3. Epub 2020 Feb 1. PMID: 32008086; PMCID: PMC7671996. 4. Chen LX, Ni XL, Zhang H, Wu M, Liu J, Xu S, Yang LL, Fu SZ, Wu J. Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer. Int J Nanomedicine. 2018 Apr 23;13:2463-2476. doi: 10.2147/IJN.S159327. PMID: 29719394; PMCID: PMC5922239.
In vitro protocol: 1. Shimizu M, Tachikawa S, Saitoh N, Nakazono K, Yu-Jung L, Suga M, Ohnuma K. Thalidomide affects limb formation and multiple myeloma related genes in human induced pluripotent stem cells and their mesoderm differentiation. Biochem Biophys Rep. 2021 Mar 13;26:100978. doi: 10.1016/j.bbrep.2021.100978. PMID: 33763605; PMCID: PMC7973312. 2. Liao H, Li Y, Zhang X, Zhao X, Zheng D, Shen D, Li R. Protective Effects of Thalidomide on High-Glucose-Induced Podocyte Injury through In Vitro Modulation of Macrophage M1/M2 Differentiation. J Immunol Res. 2020 Aug 27;2020:8263598. doi: 10.1155/2020/8263598. PMID: 32908940; PMCID: PMC7474395.
In vivo protocol: 1. Tang CT, Zhang QW, Wu S, Tang MY, Liang Q, Lin XL, Gao YJ, Ge ZZ. Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation. Cell Mol Life Sci. 2020 Dec;77(24):5207-5221. doi: 10.1007/s00018-020-03465-3. Epub 2020 Feb 1. PMID: 32008086; PMCID: PMC7671996. 2. Chen LX, Ni XL, Zhang H, Wu M, Liu J, Xu S, Yang LL, Fu SZ, Wu J. Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer. Int J Nanomedicine. 2018 Apr 23;13:2463-2476. doi: 10.2147/IJN.S159327. PMID: 29719394; PMCID: PMC5922239.

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