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Results for "

hydrophobic pocket binding

" in MedChemExpress (MCE) Product Catalog:

By Targets:	Adenylate Cyclase (1) Aldehyde Dehydrogenase (ALDH) (1) Anaplastic lymphoma kinase (ALK) (2) Apoptosis (3) Aurora Kinase (1) Autophagy (1) Bacterial (2) CD1 (1) CDK (1) Checkpoint Kinase (Chk) (1) EGFR (1) Endogenous Metabolite (1) Epigenetic Reader Domain (1) Fat Mass and Obesity-associated Protein (FTO) (1) Ferroptosis (1) Fluorescent Dye (1) Glyoxalase (GLO) (1) HIV (1) HyT (2) MDM-2/p53 (1) Nucleoside Antimetabolite/Analog (1) Orphan Nuclear Receptor (2) PD-1/PD-L1 (1) PKC (1) PPAR (1) Pyruvate Kinase (1) RAR/RXR (1) Ras (1) Reactive Oxygen Species (ROS) (1) Reverse Transcriptase (1) Tyrosinase (1) VEGFR (1)
By Research Areas:	Cancer (12) Cardiovascular Disease (2) Endocrinology (1) Infection (5) Inflammation/Immunology (2) Metabolic Disease (2) Neurological Disease (2)

By Targets:

Adenylate Cyclase (1)

Aldehyde Dehydrogenase (ALDH) (1)

Anaplastic lymphoma kinase (ALK) (2)

Apoptosis (3)

Aurora Kinase (1)

Autophagy (1)

Bacterial (2)

CD1 (1)

CDK (1)

Checkpoint Kinase (Chk) (1)

EGFR (1)

Endogenous Metabolite (1)

Epigenetic Reader Domain (1)

Fat Mass and Obesity-associated Protein (FTO) (1)

Ferroptosis (1)

Fluorescent Dye (1)

Glyoxalase (GLO) (1)

HIV (1)

HyT (2)

MDM-2/p53 (1)

Nucleoside Antimetabolite/Analog (1)

Orphan Nuclear Receptor (2)

PD-1/PD-L1 (1)

PKC (1)

PPAR (1)

Pyruvate Kinase (1)

RAR/RXR (1)

Ras (1)

Reactive Oxygen Species (ROS) (1)

Reverse Transcriptase (1)

Tyrosinase (1)

VEGFR (1)

By Research Areas:

Cancer (12)

Cardiovascular Disease (2)

Endocrinology (1)

Infection (5)

Inflammation/Immunology (2)

Metabolic Disease (2)

Neurological Disease (2)

Inhibitors & Agonists

Screening Libraries

Fluorescent Dyes

Natural
Products

Targets Recommended: Emopamil Binding Protein Cdc42-binding kinase FKBP YB-1 Penicillin-binding protein (PBP) ATP-binding cassette (ABC) transporters FABP Oxysterol-binding Protein-related Protein (ORP) Transthyretin (TTR) Ligands for Target Protein for PROTAC SDCBP GHR P-glycoprotein

Cat. No.	Product Name	Target	Research Areas	Chemical Structure

HY-147411

Ulonivirine MK-8507	Reverse Transcriptase HIV	Infection
Ulonivirine is an orally active non-nucleoside HIV-1 reverse transcriptase inhibitor that binds to the classical non-nucleoside reverse transcriptase inhibitor hydrophobic binding pocket adjacent to the polymerase active site of HIV-1 reverse transcriptase. Ulonivirine can be used in studies related to HIV-1 infection .

HY-N2204

Swertiajaponin	Tyrosinase Reactive Oxygen Species (ROS)	Inflammation/Immunology
Swertiajaponin is a tyrosinase inhibitor, forms multiple hydrogen bonds and hydrophobic interactions with the binding pocket of tyrosinase, with an IC₅₀ of 43.47 μM. Swertiajaponin also inhibits oxidative stress-mediated MAPK/MITF signaling, leading to decrease in tyrosinase protein level. Swertiajaponin suppresses melanin accumulation and exhibits strong anti-oxidative activity .

HY-D1190

DC271	RAR/RXR	Others
DC271 is a RAR agonist and synthetic retinoid that binds to the retinoid-binding site of cellular retinoic acid-binding protein II (CRBP-II). DC271 exhibits solvatochromic fluorescence properties: it produces intense blue-shifted emission in nonpolar environments and weak red-shifted emission in polar environments, and its severe fluorescence quenching in aqueous solutions can be reversed by embedding in the hydrophobic retinoid-binding protein pocket. DC271 enables direct detection of the binding between unlabeled compounds and related retinoid-binding proteins via fluorescence competition assays (Ex/Em = 355 nm/460 nm) .

HY-N15451

Deoxytopsentin	Pyruvate Kinase	Infection
Deoxytopsentin (compound 5) is a marine bisindole alkaloid and also a MRSA pyruvate kinase inhibitor. Deoxytopsentin exists in sponges. Deoxytopsentin exhibits antibacterial activity against methicillin-resistant Staphylococcus aureus strains in vitro .

HY-121900

LT175	PPAR	Metabolic Disease Endocrinology
LT175, a dual PPARα/γ ligand, is an orally active partial agonist against PPARγ(hPPARα:EC₅₀=0.22 μm; mPPARα:EC₅₀=0.26 μm; hPPARγ:EC₅₀=0.48 μm). LT175 interacts with PPARγ and affects the recruitment of the coregulators cyclic-AMP response element-binding protein-binding protein and nuclear corepressor 1 (NCoR1). LT175 interacts with PPARγ in a hydrophobic region called “diphenyl pocket”. LT175 has potent insulin-sensitizing effects and reduced adipogenic properties .

HY-164523

PV1162	Checkpoint Kinase (Chk)	Cancer
PV1162 is a selective Chk2 inhibitor with an IC₅₀ of 0.29 nM. PV1162 inhibits ATP binding to Chk2 by targeting the gatekeeper-dependent hydrophobic pocket, which is specific to Chk2 and located behind the ATP-binding site (adenine-binding region), thereby inhibiting the phosphorylation activity of Chk2. PV1162 holds potential application value in the field of cancer therapy .

HY-178343

Aurora A-IN-5	Aurora Kinase Apoptosis	Cancer
Aurora A-IN-5 is a potent and highly selective Aurora A inhibitor (IC₅₀ = 0.02 μM), showing 362-fold selectivity for over Aurora B. Aurora A-IN-5 shows its selectivity through unique C−H/π interactions, enhanced hydrophobic contacts, an open binding pocket, and tighter protein packing. Aurora A-IN-5 suppresses Aurora A autophosphorylation, thereby inhibiting cancer cell proliferation by inducing G2/M phase arrest, triggering apoptosis, and suppressing colony formation. Aurora A-IN-5 inhibits tumor growth in MDA-MB-231 xenograft mouse models. Aurora A-IN-5 can be used for breast, cervical, prostate, and lymphoma cancer research .

HY-172597

YL-1-9	MDM-2/p53 CDK Apoptosis	Cancer
YL-1-9 is an inhibitor of the degradation of p53 by MDM2 through strong binding to the key hydrophobic pockets of MDM2. YL-1-9 induces cell cycle arrest and apoptosis in breast cancer cells .

HY-126230

PAT-494	Endogenous Metabolite	Others
PAT-494 is an ATX inhibitor with significant activity in biochemical and plasma assays. PAT-494 can reduce LPA levels in rat plasma through oral administration. The structure-activity relationship study of PAT-494 shows that its binding mode with ATX is novel and it can effectively occupy the hydrophobic pockets and channels of ATX .

HY-164645

pan-KRAS-IN-16	Ras	Cancer
pan-KRAS-IN-16 (Compound 3344) is an anti-RAS small molecule derived from an intracellular antibody fragment with pan-RAS-effector protein-protein interaction inhibitor properties. pan-KRAS-IN-16 binds to a hydrophobic pocket near to the effector-binding switch regions of RAS. pan-KRAS-IN-16 prevents endogenous RAS-dependent signaling in tumor cell lines .

HY-156405

FTO-IN-10	Fat Mass and Obesity-associated Protein (FTO) Autophagy	Metabolic Disease
FTO-IN-10 (compound 7) is a potent human demethylase FTO (the fat mass and obesity-associated protein) inhibitor with an IC₅₀ of 4.5 μM. FTO-IN-10 enters the FTO’s structural domain II binding pocket through hydrophobic and hydrogen bonding interactions. FTO-IN-10 induces DNA damage and autophagic cell death in A549 cells .

HY-159920

PSB-22269	Orphan Nuclear Receptor	Neurological Disease Inflammation/Immunology
PSB-22269 is a GPR17 antagonist with a K_i value of 8.91 nM. PSB-22269 further demonstrated significant inhibitory effects in cAMP and G protein activation assays. Molecular docking studies revealed that the binding site of PSB-22269 contains positively charged arginine residues and a hydrophobic pocket. PSB-22269 provides a strategy to promote remyelination and holds promise for research in the field of multiple sclerosis .

HY-182057

ALK degrader 4	HyT Anaplastic lymphoma kinase (ALK)	Cancer
ALK degrader 4 is a ALK HyT degrader with an IC₅₀ of 0.74 nM. ALK degrader 4 inhibits ALK kinase activity, increases the solvent-accessible surface area of hydrophobic residues near the ALK binding pocket, promotes ALK to form a partially unfolded conformation, and induces proteasomal degradation of ALK. ALK degrader 4 inhibits cancer cell proliferation. ALK degrader 4 can be used in research related to non-small cell lung cancer (ALK ligand: Brigatinib (HY-12857); hydrophobic tag: Norbornene (HY-W013021)) .

HY-W170126

CB6513745	Bacterial	Infection
CB6513745 is a MelF flavin-dependent oxidoreductase inhibitor with a K_i of 18 μM against Mycobacterium marinum MelF. CB6513745 inhibits the activity of MelF flavin-dependent oxidoreductase via hydrophobic interactions with the binding pocket of the protein. CB6513745 is applicable to research related to tuberculosis .

HY-182306

VEGFR-2 ligand-2	VEGFR	Cardiovascular Disease
VEGFR-2 ligand-1, Sorafenib (HY-10201) derivative, is a vascular endothelial growth factor receptor 2 (VEGFR2) ligand. VEGFR-2 ligand-1 binds to the ATP-binding pocket of VEGFR2, forms hydrophobic contacts and hydrogen bonds with key binding-site residues. VEGFR-2 ligand-1 can be used for the research angiogenesis-related pathologies .

HY-137744

MANT-GppNHp	Adenylate Cyclase Nucleoside Antimetabolite/Analog	Infection
MANT-GppNHp is a competitive adenyl cyclase (AC) inhibitor. MANT-GppNHp is a fluorescently labeled GTP (HY-113225) analogue. MANT-GppNHp interacts with the hydrophobic pocket near the AC catalytic site through its MANT group, thereby directly blocking the binding of the substrate ATP. MANT-GppNHp can be used to study diseases related to the increased activity of AC (such as cholera) .

HY-182087

ALK degrader 3	HyT Anaplastic lymphoma kinase (ALK)	Cancer
ALK degrader 3 is a ALK HyT degrader with an IC₅₀ of 1.2 nM. ALK degrader 3 inhibits ALK kinase activity, increases the solvent-accessible surface area of hydrophobic residues near the ALK binding pocket, promotes ALK to form a partially unfolded conformation, and drives ALK degradation via the proteasomal pathway. ALK degrader 3 inhibits the proliferation of tumor cells. ALK degrader 3 can be used for the research of non-small cell lung cancer. (ALK ligand: Brigatinib (HY-12857); hydrophobic tag: Tetraasterane (HY-W1139353)) .

HY-D2939

BGSBD	Fluorescent Dye	Others
BGSBD is a SNAP-tag-based fluorescent probe (Ex/Em: 435 nm/516 nm) based on the environmentally sensitive fluorescent group SBD, specifically designed for protein labeling of live cells without washing. BGSBD achieves a 280-fold fluorescence enhancement after labeling by ingeniously utilizing the hydrophobic binding pocket of the SNAP-tag protein, providing an ideal tool for real-time monitoring of protein dynamics within cells .

HY-182020

LpxH-IN-3	Bacterial	Infection
LpxH-IN-3 is a Klebsiella pneumoniae LpxH inhibitor with an IC₅₀ of 0.17 μM. LpxH-IN-3 binds to the L-shaped hydrophobic binding pocket of Klebsiella pneumoniae LpxH, forms hydrogen bonds and other interactions with key residues, disrupts lipid A biosynthesis, and induces bacterial death. LpxH-IN-3 exhibits moderate antibacterial activity against Klebsiella pneumoniae and Escherichia coli. LpxH-IN-3 can be used for the research of klebsiella pneumoniae infection .

HY-W173361

CBP/p300-IN-24	Epigenetic Reader Domain	Others
CBP/p300-IN-24 is a selective CBP bromodomain inhibitor with an IC₅₀ of 32 μM, showing selectivity over BRD4 BD-1 bromodomain. CBP/p300-IN-24 binds to the acetyl lysine binding pocket, forms hydrogen bonds with Asn1168 and a solvent-mediated hydrogen bond with Tyr1125, and forms hydrophobic interactions with Leu1120, Ile1122, and Val1174 .

HY-18314B

(Z)-GW 441756	Orphan Nuclear Receptor Ferroptosis	Cardiovascular Disease
(Z)-GW 441756 is a hepatocyte nuclear factor 4α (HNF4α) activator, with an EC₅₀ of 9.2 μM and a K_a of 4.6 μM in human systems. (Z)-GW 441756 directly interacts with the ligand-binding domain of HNF4α via persistent hydrogen bonds and hydrophobic interactions within the binding pocket. (Z)-GW 441756 reduces the accumulation of triglycerides and total cholesterol. (Z)-GW 441756 inhibits ferroptosis through a non-antioxidant mechanism. (Z)-GW 441756 decreases plasma triglyceride and total cholesterol levels in animal models of hyperlipidemia. (Z)-GW 441756 can be used in studies related to hyperlipidemia .

HY-181739

GCB-27a	CD1	Cancer
GCB-27a is a *CD1d*-binding immunostimulant and antitumor agent. GCB-27a binds to CD1d to form a stable complex and presents it to NKT cells, enhancing hydrophobic interactions within the A' pocket of CD1d through branched-chain conformation restriction. GCB-27a induces a Th1-biased immune response, drives IFN?γ production and limits IL-4 levels. GCB-27a is applicable to research related to melanoma lung metastasis .

HY-130305A

GSK-943949A	PKC	Cancer
GSK-943949A is a PRK1 inhibitor with an IC₅₀ of 40.0 nM. GSK-943949A is applicable to research related to prostate cancer .

HY-128299

ALDH3A1-IN-4	Aldehyde Dehydrogenase (ALDH)	Neurological Disease Cancer
ALDH3A1-IN-4 is a selective ALDH3A1 inhibitor with an IC₅₀ of 0.2 μM. ALDH3A1-IN-4 binds to the aldehyde-binding pocket of ALDH3A1 via hydrophobic interactions and van der Waals forces. ALDH3A1-IN-4 acts as a chemosensitizer that sensitizes ALDH3A1-expressing cancer cells to the antiproliferative effect of mafosfamide, but does not produce a sensitizing effect on non-cancer cells that do not express ALDH3A1. ALDH3A1-IN-4 is applicable to research related to lung adenocarcinoma and glioblastoma .

HY-181954

ZW-49	EGFR Apoptosis	Cancer
ZW-49 is an orally active pan-EGFR inhibitor with IC₅₀ values at 0.03-1.5 nM. ZW-49 inhibits all subgroups of EGFR mutations with selectivity over wild-type EGFR and other target families. ZW-49 blocks the ATP-binding pocket, occupies a conserved hydrophobic subpocket, avoids steric conflicts with PACC mutation P loops. ZW-49 inhibits cancer cells proliferation, induces G0/G1 phase cell-cycle arrest and apoptosis, and demonstrates anti-proliferative activity in xenograft mice models. ZW-49 can be used for the research of cancer, such as non-small cell lung cancer .

HY-182047

PD-1/PD-L1-IN-61	PD-1/PD-L1	Cancer
PD-1/PD-L1-IN-61 is a PD-1/PD-L1 interaction inhibitor with a human IC₅₀ of 5.3 nM. PD-1/PD-L1-IN-61 embeds into the hydrophobic pocket at the PD-L1 dimer interface, stabilizing binding through hydrogen bonds and π-π stacking with PD-L1 residues. PD-1/PD-L1-IN-61 acts as an immune activator, enhances immune-killing activity of peripheral blood mononuclear cells against cancer cells, restores T-cell immune function, and promotes IFN-γ secretion. PD-1/PD-L1-IN-61 can be used for the research of triple-negative breast cancer .

HY-181980

SPB07393SC	Glyoxalase (GLO)	Cancer
SPB07393SC is a glyoxalase-I (Glo-I) inhibitor with an IC₅₀ of 11.1 μM. SPB07393SC is applicable for cancer research .

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-L928

GPCR Targeted Diversity Library	7,113 compounds
G protein-coupled receptors (GPCRs) are membrane proteins in humans and one of the most important targets in drug discovery. Approximately 35% of launched drugs are targeted GPCRs, making them a crucial class of targets in drug discovery. The orthosteric site of a GPCR is its endogenous ligand’s (such as neurotransmitters or hormones) binding site. This site plays a central role in signal transduction. Small molecules binding to this site typically contain a protonatable amino group, enabling the formation of salt bridges or hydrogen bonds with acidic residues in the binding pocket. In contrast, the allosteric site does not directly initiate signaling but modulates the signal intensity of the GPCR by altering or stabilizing the conformation of the orthosteric site. Small molecules binding to the allosteric site often contain multiple aromatic rings to occupy hydrophobic pockets and achieve their functional effects. MCE has collected over 7,113 reported bioactive molecules targeting GPCRs, covering Class A, B, and C GPCRs. These small molecules were subjected to AI representation to extract 2D and 3D features. Subsequently, we do screening by AI score based on similarity to identify molecules in diversity library highly similar to the reported bioactive molecules in both 2D and 3D, with a threshold greater than 0.7. Further screening based on cLogP was applied to select molecules with good lipophilicity, which facilitates the binding of small molecules to GPCRs. This diversity library can be widely applied to the discovery of compounds targeting GPCR proteins.

GPCR Targeted Diversity Library

7,113 compounds

G protein-coupled receptors (GPCRs) are membrane proteins in humans and one of the most important targets in drug discovery. Approximately 35% of launched drugs are targeted GPCRs, making them a crucial class of targets in drug discovery.

The orthosteric site of a GPCR is its endogenous ligand’s (such as neurotransmitters or hormones) binding site. This site plays a central role in signal transduction. Small molecules binding to this site typically contain a protonatable amino group, enabling the formation of salt bridges or hydrogen bonds with acidic residues in the binding pocket. In contrast, the allosteric site does not directly initiate signaling but modulates the signal intensity of the GPCR by altering or stabilizing the conformation of the orthosteric site. Small molecules binding to the allosteric site often contain multiple aromatic rings to occupy hydrophobic pockets and achieve their functional effects.

MCE has collected over 7,113 reported bioactive molecules targeting GPCRs, covering Class A, B, and C GPCRs. These small molecules were subjected to AI representation to extract 2D and 3D features. Subsequently, we do screening by AI score based on similarity to identify molecules in diversity library highly similar to the reported bioactive molecules in both 2D and 3D, with a threshold greater than 0.7. Further screening based on cLogP was applied to select molecules with good lipophilicity, which facilitates the binding of small molecules to GPCRs. This diversity library can be widely applied to the discovery of compounds targeting GPCR proteins.

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.

Cat. No.	Product Name	Type

HY-D1190

DC271	Fluorescent Dyes
DC271 is a RAR agonist and synthetic retinoid that binds to the retinoid-binding site of cellular retinoic acid-binding protein II (CRBP-II). DC271 exhibits solvatochromic fluorescence properties: it produces intense blue-shifted emission in nonpolar environments and weak red-shifted emission in polar environments, and its severe fluorescence quenching in aqueous solutions can be reversed by embedding in the hydrophobic retinoid-binding protein pocket. DC271 enables direct detection of the binding between unlabeled compounds and related retinoid-binding proteins via fluorescence competition assays (Ex/Em = 355 nm/460 nm) .

DC271

Fluorescent Dyes

DC271 is a RAR agonist and synthetic retinoid that binds to the retinoid-binding site of cellular retinoic acid-binding protein II (CRBP-II). DC271 exhibits solvatochromic fluorescence properties: it produces intense blue-shifted emission in nonpolar environments and weak red-shifted emission in polar environments, and its severe fluorescence quenching in aqueous solutions can be reversed by embedding in the hydrophobic retinoid-binding protein pocket. DC271 enables direct detection of the binding between unlabeled compounds and related retinoid-binding proteins via fluorescence competition assays (Ex/Em = 355 nm/460 nm) .

HY-D2939

BGSBD	Fluorescent Dyes
BGSBD is a SNAP-tag-based fluorescent probe (Ex/Em: 435 nm/516 nm) based on the environmentally sensitive fluorescent group SBD, specifically designed for protein labeling of live cells without washing. BGSBD achieves a 280-fold fluorescence enhancement after labeling by ingeniously utilizing the hydrophobic binding pocket of the SNAP-tag protein, providing an ideal tool for real-time monitoring of protein dynamics within cells .

BGSBD

Fluorescent Dyes

BGSBD is a SNAP-tag-based fluorescent probe (Ex/Em: 435 nm/516 nm) based on the environmentally sensitive fluorescent group SBD, specifically designed for protein labeling of live cells without washing. BGSBD achieves a 280-fold fluorescence enhancement after labeling by ingeniously utilizing the hydrophobic binding pocket of the SNAP-tag protein, providing an ideal tool for real-time monitoring of protein dynamics within cells .

Swertiajaponin	Flavonoids other families Classification of Application Fields Flavones Phenols Polyphenols Plants Inflammation/Immunology Disease Research Fields Source Classification	Tyrosinase Reactive Oxygen Species (ROS)
Swertiajaponin is a tyrosinase inhibitor, forms multiple hydrogen bonds and hydrophobic interactions with the binding pocket of tyrosinase, with an IC₅₀ of 43.47 μM. Swertiajaponin also inhibits oxidative stress-mediated MAPK/MITF signaling, leading to decrease in tyrosinase protein level. Swertiajaponin suppresses melanin accumulation and exhibits strong anti-oxidative activity .

Deoxytopsentin	Structural Classification Alkaloids Marine natural products Sponge Indole Alkaloids Source Classification	Pyruvate Kinase
Deoxytopsentin (compound 5) is a marine bisindole alkaloid and also a MRSA pyruvate kinase inhibitor. Deoxytopsentin exists in sponges. Deoxytopsentin exhibits antibacterial activity against methicillin-resistant Staphylococcus aureus strains in vitro .

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hydrophobic pocket binding

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