MilliporeSigma
  • Home
  • Search Results
  • An updated steroid benchmark set and its application in the discovery of novel nanomolar ligands of sex hormone-binding globulin.

An updated steroid benchmark set and its application in the discovery of novel nanomolar ligands of sex hormone-binding globulin.

Journal of medicinal chemistry (2008-03-12)
Artem Cherkasov, Fuqiang Ban, Osvaldo Santos-Filho, Nels Thorsteinson, Magid Fallahi, Geoffrey L Hammond
ABSTRACT

A benchmark data set of steroids with known affinity for sex hormone-binding globulin (SHBG) has been widely used to validate popular molecular field-based QSAR techniques. We have expanded the data set by adding a number of nonsteroidal SHBG ligands identified both from the literature and in our previous experimental studies. This updated molecular set has been used herein to develop 4D QSAR models based on "inductive" descriptors and to gain insight into the molecular basis of protein-ligand interactions. Molecular alignment was generated by means of docking active compounds into the active site of the SHBG. Surprisingly, the alignment of the benchmark steroids contradicted the classical ligand-based alignment utilized in previous CoMFA and CoMSIA models yet afforded models with higher statistical significance and predictive power. The resulting QSAR models combined with CoMFA and CoMSiA models as well as structure-based virtual screening allowed discovering several low-micromolar to nanomolar nonsteroidal inhibitors for human SHBG.

MATERIALS
Product Number
Brand
Product Description

Supelco
4-tert-Octylphenol, analytical standard
Sigma-Aldrich
4-tert-Octylphenol, 97%
Supelco
Progesterone, VETRANAL®, analytical standard
Sigma-Aldrich
17α-Methyltestosterone, solid (photosensitive)
Sigma-Aldrich
19-Nortestosterone
Sigma-Aldrich
β-Estradiol, BioReagent, powder, suitable for cell culture
Sigma-Aldrich
β-Estradiol, analytical standard
Sigma-Aldrich
17α-Ethynylestradiol, ≥98%
Sigma-Aldrich
β-Estradiol, powder, γ-irradiated, suitable for cell culture
Sigma-Aldrich
β-Estradiol 3-benzoate, ≥97%
Sigma-Aldrich
Genistein, synthetic, ≥98% (HPLC), powder
Sigma-Aldrich
Genistein, from Glycine max (soybean), ~98% (HPLC)
Sigma-Aldrich
Reichstein′s substance S, ≥98%
Sigma-Aldrich
19-Norethindrone, ≥98%, powder
Sigma-Aldrich
5α-Androstane-3α,17β-diol
Sigma-Aldrich
Progesterone, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Progesterone, ≥99%
Supelco
D(−)-Norgestrel, analytical standard
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Supelco
17α-Methylandrostan-17β-ol-3-one, analytical standard
Sigma-Aldrich
trans-Dehydroandrosterone, ≥99%
Sigma-Aldrich
Progesterone, meets USP testing specifications
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Corticosterone, ≥92%
Sigma-Aldrich
Hydrocortisone-Water Soluble, BioReagent, suitable for cell culture
Sigma-Aldrich
Etiocholan-3α-ol-17-one
Sigma-Aldrich
β-Estradiol, ≥98%
Sigma-Aldrich
Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
Progesterone, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture