(S)-Thalidomide
(Synonyms: (S)-(-)-Thalidomide) 目录号 : GC66064
An active enantiomer of (±)-thalidomide
Cas No.:841-67-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
(–)-Thalidomide is an active enantiomer of (±)-thalidomide and has immunomodulatory and teratogenic activities.1,2,3 It enhances TNF-α production induced by phorbol 12-myristate 13-acetate in HL-60 cells when used at concentrations ranging from 0.1 to 100 ?M.1 Preincubation of isolated Rhode Island Red (RIR) chicken donor blood with (–)-thalidomide (10 mg/ml) reduces recipient chicken embryo splenomegaly in a model of graft versus host disease.2 (–)-Thalidomide (150 mg/kg) induces fetal malformations when administered to pregnant female rabbits.3
1.Nishimura, K., Hashimoto, Y., and Iwasaki, S.(S)-form of α -methyl-N( α )-phthalimidoglutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-α production by human leukemia cell HL-60: Implication of optical resolution of thalidomidal effectsChem. Pharm. Bull. (Tokyo)42(5)1157-1159(1994) 2.Field, E.O., Gibbs, J.E., Tucker, D.F., et al.Effect of thalidomide on the graft versus host reactionNature211(5055)1308-1310(1966) 3.Fabro, S., Smith, R.L., and Williams, R.T.Toxicity and teratogenicity of optical isomers of thalidomideNature215(5098)296(1967)
| Cas No. | 841-67-8 | SDF | Download SDF |
| 别名 | (S)-(-)-Thalidomide | ||
| 分子式 | C13H10N2O4 | 分子量 | 258.23 |
| 溶解度 | DMSO : 83.33 mg/mL (322.70 mM; Need ultrasonic) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8725 mL | 19.3626 mL | 38.7252 mL |
| 5 mM | 0.7745 mL | 3.8725 mL | 7.745 mL |
| 10 mM | 0.3873 mL | 1.9363 mL | 3.8725 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Towards understanding the interaction of (S)-Thalidomide with nucleobases
Arch Biochem Biophys 2020 Oct 30;693:108566.PMID:32896516DOI:10.1016/j.abb.2020.108566.
Interaction of (S)-Thalidomide molecule with four nucleobases: adenine, guanine, cytosine and thymine, is investigated in details employing density functional theory methods. Different mutual positions of the molecules are considered, with the starting geometries enabling hydrogen bond interactions between the monomers. Optimization of geometrical parameters is carried out within the B3LYP/6-311G** approximation and followed by evaluation of vibrational frequencies. Binding and interaction energies are calculated employing exchange-correlation functionals including long-range corrections and properly diffuse basis sets. The strongest interaction exists within the (S)-thalidomide-guanine complex. Interestingly, in one of the investigated (S)-thalidomide-guanine complexes two bifurcated hydrogen bonds are observed. The two hydrogens involved in one of them are bonded to a carbon atom in the α position relative to carbonyl group. The present study can be useful in the design of new anticancer and antiviral drugs interacting selectively with DNA or RNA.
Molecular glue CELMoD compounds are regulators of cereblon conformation
Science 2022 Nov 4;378(6619):549-553.PMID:36378961DOI:10.1126/science.add7574.
Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically relevant proteins for degradation. Prior crystallographic studies defined the drug-binding site within CRBN'S thalidomide-binding domain (TBD), but the allostery of drug-induced neosubstrate binding remains unclear. We performed cryo-electron microscopy analyses of the DNA damage-binding protein 1 (DDB1)-CRBN apo complex and compared these structures with DDB1-CRBN in the presence of CELMoD compounds alone and complexed with neosubstrates. Association of CELMoD compounds to the TBD is necessary and sufficient for triggering CRBN allosteric rearrangement from an open conformation to the canonical closed conformation. The neosubstrate Ikaros only stably associates with the closed CRBN conformation, illustrating the importance of allostery for CELMoD compound efficacy and informing structure-guided design strategies to improve therapeutic efficacy.
Enantioselective sensing of (S)-Thalidomide in blood plasma with a chiral naphthalene diimide derivative
Biosens Bioelectron 2020 Nov 1;167:112446.PMID:32818748DOI:10.1016/j.bios.2020.112446.
Fast, simple in use and highly effective voltammetric enantiosensor dedicated for determination of thalidomide (TD) enantiomers (especially towards the toxic (S)-enantiomer) in blood plasma is still desirable. Here we have proven that newly synthesized chiral naphthalene diimide (NDI) derivatives are excellent electroactive materials for TD enantiosensors. The recognition process relies on the specific interaction between the chiral NDI receptor and the thalidomide enantiomer of the opposite configuration. This unique specific interaction between (S)-Thalidomide and (R)-NDI derivative counterparts, evident in the DPV voltammograms, was confirmed by molecular modeling. The demonstrated voltammetric enantiosensors are characterized by the low detection limit at the level of μg·L-1, wide analytical range from 5·10-4 - 10 mg·L-1, high selectivity and long lifetime. The results of the recovery rates showed a very good degree of accuracy towards the determination of (S)-Thalidomide in the blood samples, so it can be successfully used in the analysis of clinical samples.
Clinical pharmacology of thalidomide
Eur J Clin Pharmacol 2001 Aug;57(5):365-76.PMID:11599654DOI:10.1007/s002280100320.
Background: Thalidomide has a chiral centre, and the racemate of (R)- and (S)-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 due to its unique anti-inflammatory and immunomodulatory effects. Objective: To critically review pharmacokinetic studies and briefly review pharmacodynamic effects and studies of thalidomide in consideration of its chemical and stereochemical properties and metabolism. Methods: Literature search and computer simulations of pharmacokinetics. Results: Rational use of thalidomide is problematic due to lack of basic knowledge of its mechanism of action, effects of the separate enantiomers and metabolites and dose- and concentration-effect relationships. Due to its inhibition of tumour necrosis factor-alpha and angiogenesis, racemic thalidomide has been tested with good effect in a variety of skin and mucous membrane disorders, Crohn's disease, graft-versus-host disease, complications to human immunodeficiency virus and, recently, in multiple myeloma. Adverse reactions are often related to the sedative effects. Irreversible toxic peripheral neuropathy and foetal malformations are serious complications that can be prevented. The results of several published pharmacokinetic studies can be questioned due to poor methodology and the use of non-stereospecific assays. The enantiomers of thalidomide undergo spontaneous hydrolysis and fast chiral interconversion at physiological pH. The oral bioavailability of thalidomide has not been unequivocally determined, but available data suggest that it is high. Absorption is slow, with a time to maximum plasma concentration of at least 2 h, and may also be dose-dependent; however, that of the separate enantiomers may be faster due to higher aqueous solubility. Estimation of the volume of distribution is complicated by probable hydrolysis and chiral inversion also in peripheral compartments. A value of around 11/kg is however plausible. Plasma protein binding is low with little difference between the enantiomers. Elimination of thalidomide is mainly by pH-dependent spontaneous hydrolysis in all body fluids with an apparent mean clearance of 10 l/h for the (R)- and 21 l/h for the (S)-enantiomer in adult subjects. Blood concentrations of the (R)-enantiomer are consequently higher than those of the (S)-enantiomer at pseudoequilibrium. The mean elimination half-life of both enantiomers is 5 h. One hydroxylated metabolite has been found in low concentrations in the blood. Since both enzymatic metabolism and renal excretion play minor roles in the elimination of thalidomide, the risk of drug interactions seems to be low. Conclusions: The interest in and use of thalidomide is increasing due to its potential as an immunomodulating and antiangiogenic agent. The inter-individual variability in distribution and elimination is low. Apart from this, its use is complicated by the lack of knowledge of dose- or concentration-effect relationships, possible dose-dependent oral absorption and of course by its well-known serious adverse effects.
Recent advances in analytical determination of thalidomide and its metabolites
J Pharm Biomed Anal 2008 Jan 7;46(1):9-17.PMID:18023317DOI:10.1016/j.jpba.2007.10.003.
Thalidomide, a racemate, is coming into clinical use as immuno-modulating and anti-inflammatory drug. Thalidomide was approved by the FDA in July 1998 for the treatment of erythema nodusum leprosum associated with leprosy. Recently, thalidomide is proving to be a promising drug in the treatment of a number of cancers and inflammatory diseases, such as multiple myeloma, inflammatory bowel disease (Crohn'S disease), HIV and cancer associated cachexia. These effects may chiefly be exerted by S-thalidomide, but the enantiomers are inter-converted in vivo. Thalidomide is given orally, although parenteral administration would be desirable in some clinical situations. Thalidomide has been determined in formulations and, principally in biological fluids by a variety of methods such as high-performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The overview includes the most relevant analytical methodologies used in its determination.