Search Result

Results for "

cryptic pocket

" in MedChemExpress (MCE) Product Catalog:

By Targets:	Casein Kinase (1) CDK (1) FBPase (1) LAG-3 (1) Ser/Thr Protease (1) Serpin (1)
By Research Areas:	Cancer (2) Inflammation/Immunology (1) Metabolic Disease (2)

Inhibitors & Agonists

Screening Libraries

Cat. No.	Product Name	Target	Research Areas	Chemical Structure

HY-159805

CDK2-IN-31	CDK	Cancer
CDK2-IN-31 is a CCNE1:CDK2 complex inhibitor with an IC₅₀ of 0.13 μM. CDK2-IN-31 binds to a cryptic allosteric pocket at the CCNE1:CDK2 interface, inducing structural rearrangements of the CDK2 A-loop that disrupt the kinase's active conformation and interfere with substrate binding. CDK2-IN-31 inhibits phosphorylation of retinoblastoma protein 1 (RB1) in CCNE1-dependent ovarian cancer cells. CDK2-IN-31 impairs coenrichment of protein PRC1 with CCNE1-N112C:CDK2 complexes. CDK2-IN-31 can be used for the research of ovarian cancer .

HY-134858

GSK716 A1AT modulator 1	Serpin Ser/Thr Protease	Metabolic Disease
GSK716 (A1AT modulator 1) is an orally active Z α₁-antitrypsin (Z-A1AT) inhibitor with a pIC₅₀ of 8.3. GSK716 binds a cryptic Z α₁-antitrypsin pocket, stabilizes monomeric folding intermediates, blocks polymerization, and increases monomer secretion. GSK716 acts on select sensitive α₁-antitrypsin variants but fails to affect resistant variants. GSK716 can be used for the research of α₁-antitrypsin deficiency and α₁-antitrypsin deficiency-associated liver disease .

HY-123853

CAM4066	Casein Kinase	Cancer
CAM4066 is a potent CK2α inhibitor, with an IC₅₀ value of 300 nM. CAM4066 exhibits high selectivity, with IC₅₀ values of 22.35, 43.55, and > 50 μM for HIPK3, DAPK3, and CLK2, respectively. CAM4066 shows no cell activity. CAM4066 can be used for the development of highly potent CK2 inhibitors .

HY-182346

FBPase-IN-7	FBPase	Metabolic Disease
FBPase-IN-7 is a fructose-1,6-bisphosphatase (FBPase) inhibitor with an IC₅₀ of 0.75 μM. FBPase-IN-7 binds to a cryptic allosteric pocket of FBPase, induces conformational rearrangement of key residues, forms a hydrogen-bond network, and disrupts substrate catalysis. FBPase-IN-7 confirms cellular stabilizes HuFBPase in hepatic cells. FBPase-IN-7 has hypoglycemic activity. FBPase-IN-7 can be used for the research of type 2 diabetes .

HY-180900

Z3071585108	LAG-3	Inflammation/Immunology
Z3071585108 is a small molecule binder of the LAG-3 D1 domain with K_d values measured for the MST-TRIC channel and spectral shift detection of 59.2 and 56.1 μM respectively. Z3071585108 partially inhibits the binding of LAG-3 to MHCII, with an EC₅₀ of 42.9 μM. Z3071585108 can be used for the study of small molecule immunotherapies targeting LAG-3 .

Cat. No.	Product Name

HY-L942

Allosteric Modulator Fragment Library	1802 compounds
In contrast to the high conservation of conventional orthosteric sites, allosteric sites possess structural characteristics of low conservation, high hydrophobicity, weak polarity, confined spatial geometry, and dynamic cryptic properties. There is a significant difference between their core structures and orthosteric pockets — allosteric pockets are mostly dynamic grooves formed by protein conformational changes, subunit interface clefts, or shallow depressions, rather than the rigid "keyhole" structure of orthosteric sites. With looser spatial constraints, allosteric sites have the advantages of high selectivity and low off-target risk, and have become an important direction in new drug discovery. Based on the dynamic, hydrophobic, and narrow-long spatial characteristics of allosteric pockets, MCE has performed targeted modification and screening of fragments. The screening criteria strictly conform to the requirements of allosteric binding: molecular weight is controlled at 120–280 Da (to meet the core needs of small molecules in fragment libraries and high derivatization), hydrogen bond donors (HBD ≤ 2), hydrogen bond acceptors (HBA ≤ 3), polar surface area (PSA = 30–80 Å²), rotatable bonds (≤ 2), moderate hydrophobicity (cLogP = 1–3.5), no strongly ionizable groups, and both appropriate rigidity and conformational flexibility to adapt to the dynamic changes of the pocket. Meanwhile, combined with the results of principal moment of inertia (PMI) analysis, fragments with high 3D diversity were obtained. Such fragments have good shape complementarity with allosteric pockets, ensuring that the fragments can smoothly enter the allosteric pockets and form stable binding, while providing room for subsequent optimization and derivation. This library contains 1,800 structurally diverse fragment molecules with excellent drug-like properties, suitable for allosteric drug development and the design and optimization of allosteric sites. It combines the

Allosteric Modulator Fragment Library

1802 compounds

In contrast to the high conservation of conventional orthosteric sites, allosteric sites possess structural characteristics of low conservation, high hydrophobicity, weak polarity, confined spatial geometry, and dynamic cryptic properties. There is a significant difference between their core structures and orthosteric pockets — allosteric pockets are mostly dynamic grooves formed by protein conformational changes, subunit interface clefts, or shallow depressions, rather than the rigid "keyhole" structure of orthosteric sites. With looser spatial constraints, allosteric sites have the advantages of high selectivity and low off-target risk, and have become an important direction in new drug discovery.

Based on the dynamic, hydrophobic, and narrow-long spatial characteristics of allosteric pockets, MCE has performed targeted modification and screening of fragments. The screening criteria strictly conform to the requirements of allosteric binding: molecular weight is controlled at 120–280 Da (to meet the core needs of small molecules in fragment libraries and high derivatization), hydrogen bond donors (HBD ≤ 2), hydrogen bond acceptors (HBA ≤ 3), polar surface area (PSA = 30–80 Å²), rotatable bonds (≤ 2), moderate hydrophobicity (cLogP = 1–3.5), no strongly ionizable groups, and both appropriate rigidity and conformational flexibility to adapt to the dynamic changes of the pocket. Meanwhile, combined with the results of principal moment of inertia (PMI) analysis, fragments with high 3D diversity were obtained. Such fragments have good shape complementarity with allosteric pockets, ensuring that the fragments can smoothly enter the allosteric pockets and form stable binding, while providing room for subsequent optimization and derivation.

This library contains 1,800 structurally diverse fragment molecules with excellent drug-like properties, suitable for allosteric drug development and the design and optimization of allosteric sites. It combines the

HY-L941

Allosteric Modulator Lead‑like Compound Library	4315 compounds
Owing to the high conservation of orthosteric sites, conventional orthosteric drugs frequently suffer from poor subtype selectivity, off-target toxicity, and drug resistance, severely restricting their clinical application. In contrast, allosteric sites feature low conservation, high hydrophobicity, weak polarity, confined spatial geometry, and dynamic cryptic properties. These characteristics endow allosteric modulators with distinct advantages including high selectivity, functional tunability, and improved safety, making allosteric therapy a key direction in modern drug discovery. MCE has curated nearly 1,000 structurally disclosed clinical-stage allosteric modulators. By analyzing allosteric protein–ligand complex structures from the PDB database, we extracted core pharmacophores and privileged scaffolds. Adopting a rational design strategy of “scaffold derivation + allosteric physicochemical filtering”, we performed secondary screening on the derived compounds strictly following the optimal physicochemical principles for allosteric binding based on universal allosteric pocket properties: molecular weight 300–500 Da, HBD ≤ 3, HBA = 3–8, PSA = 70–120 Å², rotatable bonds ≤ 6, highly rigid scaffolds, cLogP = 1.0–3.8, and no strongly ionizable groups. The selected compounds exhibit high rigidity and shape complementarity, making them well-suited for targeting shallow, dynamic, and hydrophobic-dominated allosteric pockets. This allosteric modulator library contains 4,315 structurally diverse, lead-like compounds dedicated to allosteric drug development, allosteric site targeting, and allosteric modulator screening. It is suitable for kinases, GPCRs, and other important drug targets. All compounds are analogs of clinical-stage allosteric modulators with a similarity score > 0.6, combining excellent druggability and allosteric binding potential. It provides a highly efficient tool for early-stage allosteric drug discovery.

Allosteric Modulator Lead‑like Compound Library

4315 compounds

Owing to the high conservation of orthosteric sites, conventional orthosteric drugs frequently suffer from poor subtype selectivity, off-target toxicity, and drug resistance, severely restricting their clinical application. In contrast, allosteric sites feature low conservation, high hydrophobicity, weak polarity, confined spatial geometry, and dynamic cryptic properties. These characteristics endow allosteric modulators with distinct advantages including high selectivity, functional tunability, and improved safety, making allosteric therapy a key direction in modern drug discovery.

MCE has curated nearly 1,000 structurally disclosed clinical-stage allosteric modulators. By analyzing allosteric protein–ligand complex structures from the PDB database, we extracted core pharmacophores and privileged scaffolds. Adopting a rational design strategy of “scaffold derivation + allosteric physicochemical filtering”, we performed secondary screening on the derived compounds strictly following the optimal physicochemical principles for allosteric binding based on universal allosteric pocket properties: molecular weight 300–500 Da, HBD ≤ 3, HBA = 3–8, PSA = 70–120 Å², rotatable bonds ≤ 6, highly rigid scaffolds, cLogP = 1.0–3.8, and no strongly ionizable groups. The selected compounds exhibit high rigidity and shape complementarity, making them well-suited for targeting shallow, dynamic, and hydrophobic-dominated allosteric pockets.

This allosteric modulator library contains 4,315 structurally diverse, lead-like compounds dedicated to allosteric drug development, allosteric site targeting, and allosteric modulator screening. It is suitable for kinases, GPCRs, and other important drug targets. All compounds are analogs of clinical-stage allosteric modulators with a similarity score > 0.6, combining excellent druggability and allosteric binding potential. It provides a highly efficient tool for early-stage allosteric drug discovery.

Inquiry Online

Your information is safe with us. * Required Fields.

MCE Japan Authorized Agent ナミキ商事株式会社コスモ・バイオ株式会社重松貿易株式会社
Salutation			Country or Region *
Applicant Name *			Organization Name *
Department *
Email Address *			Product Name *
Cat. No.			Requested quantity *
Phone Number *
Remarks

Inquiry Online

Inquiry Information

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

BODIPY 493/503 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Feb 1;16(1):1241. [Abstract]

MedchemExpress Validation 01

Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred to a PVDF membrane and blocked with 5% non-fat milk in TBST for 2 hour at room temperature. The primary antibody (1/1000) and Loading control antibody (Beta Actin, HY-P80438, 1/10000) was used in 5% non-fat milk in TBST at 4°C overnight. Goat Anti-Mouse/Rabbit IgG-HRP Secondary Antibody (1/10000) was used for 1 hour at room temperature. Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred to a PVDF membrane and blocked with 5% non-fat milk in TBST for 2 hour at room temperature. The primary antibody (1/1000) and Loading control antibody (Beta Actin, HY-P80438, 1/10000) was used in 5% non-fat milk in TBST at 4°C overnight. Goat Anti-Mouse/Rabbit IgG-HRP Secondary Antibody (1/10000) was used for 1 hour at room temperature. Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred to a PVDF membrane and blocked with 5% non-fat milk in TBST for 2 hour at room temperature. The primary antibody (1/1000) and Loading control antibody (Beta Actin, HY-P80438, 1/10000) was used in 5% non-fat milk in TBST at 4°C overnight. Goat Anti-Mouse/Rabbit IgG-HRP Secondary Antibody (1/10000) was used for 1 hour at room temperature.

BODIPY 493/503 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Feb 1;16(1):1241. [Abstract]

MedchemExpress Validation 01

MedchemExpress Validation 03

Western blot analysis of extracts from THP-1(lane 2(20μg), Jurkat (lane 3(20μg) and NIH3T3(lane 4(20μg) using FOXO1A (HY-P80132) Rabbit mAb. Proteins were transferred

MedchemExpress Validation 04

MedchemExpress Validation

We use cookies

MedChemExpress values your privacy and your trust is important to us. We use cookies to enhance your website experience. Some cookies are necessary to run the website. Privacy and Cookie Policy

Name
Email *

	Sorry, but the email address you supplied was invalid.