Cat. No.: HY-115454

GB111-NH2

GB111-NH2 is a covalent cysteine cathepsin inhibitor. GB111-NH2 blocks cathepsin B/L/S activity, probe binding, and BMV109 signal in biopsy tissue. GB111-NH2 blocks brain cathepsin GB123 binding under ex vivo conditions. GB111-NH2 induces oxidative stress, autophagy inhibition, apoptosis, proliferation/S-phase entry, arginase activity, and non-autonomous apoptosis of neighboring tumor cells. GB111-NH2 reduces primary breast tumor volume, causes tumor regression, and alters macrophage morphology. GB111-NH2 restores marginal zone architecture and elevates lymphotoxin α (LTα) and splenic lymphotoxin β receptor (LTβR) signaling. GB111-NH2 can be used for research on chronic epilepsy, breast cancer, and atherosclerosis.

For research use only. We do not sell to patients.

CAS No.: 956479-18-8
Formula: C₃₃H₃₉N₃O₆
Molecular Weight:573.68

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (280 KB)

GB111-NH2 Chemical Structure

CAS No.: 956479-18-8

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

All Cathepsin Isoforms :

All TNF Receptor Isoforms :

In Vitro

ApoptosisCell Cycle RegulationInnate ImmunityLysosomal MetabolismCytokines & ChemokinesAutophagyProtein/Amino Acid Metabolism

Apoptosis

Cell Cycle Regulation

GB111-NH2 (1 μM; 2-7 days) reduces primary mouse macrophage viability, cell number, and oxidative stress on day 7, while increasing caspase-3 apoptosis, BrdU incorporation, and cell cycle markers, and effective mitosis is detectable by CFSE^[4].

Innate Immunity

Lysosomal Metabolism

GB111-NH2 blocks α-defensin-induced cathepsin activity in RAW264.7 macrophage culture medium^[6].

Innate Immunity

Lysosomal Metabolism

Cytokines & Chemokines

GB111-NH2 (1 μM) blocks cysteine cathepsin activity in primary mouse macrophages for at least 72 h and prevents the IL-4-induced increase in cathepsin B, L, and S mRNA^[4].

Lysosomal Metabolism

GB111-NH2 (1 µM; 2 h before T-GNP addition) produces potent cathepsin inhibition in 4T1 cells comparable to T-GNP alone^[1].
GB111-NH2 (5 μM; 30 min) inhibits ex vivo cathepsin labeling in mouse brain lysates and in rat and human epileptic brain tissue sections^[2].
GB111-NH2 (0.1-10 μM; 1 h) inhibits recombinant cathepsins B, L, and S more effectively than JPM-OEt (HY-102087)^[4].

Lysosomal Metabolism

Autophagy

GB111-NH2 (1 μM) inhibits autophagy in primary mouse macrophages, and LC-MS/MS reveals 495 IL-4 polarization-dependent protein changes (235 decreased, 260 increased), as well as 31, 24, and 11 unique protein changes in the comparison between the inhibition group and the control group, respectively^[4].

Protein/Amino Acid Metabolism

Lysosomal Metabolism

GB111-NH2 (1 μM; 7 days) increases arginase activity in primary mouse macrophages and alters M2 marker gene expression, cell size, and cell structure^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Anti-cancerApoptosisOxidative StressInnate ImmunityAdaptive ImmunityCytokines & ChemokinesLysosomal Metabolism

Anti-cancer

Apoptosis

Oxidative Stress

Innate Immunity

GB111-NH2 (40 mg/kg; intraperitoneal injection; once daily; 3 consecutive days) reduces primary breast tumor mass in 4T1 tumor-bearing mice by inducing oxidative stress and apoptosis in tumor-associated macrophages, accompanied by apoptosis of adjacent tumor cells^[4].

Innate Immunity

Adaptive Immunity

Cytokines & Chemokines

Lysosomal Metabolism

GB111-NH2 (1 mg/mouse, dissolved in 10% DMSO, 15% Tween 80, 75% PBS; intraperitoneal injection; two rounds of 3-day dosing followed by 3 days of saline; one week) restores marginal zone architecture and elevates LTα and LTβR signaling in TSC1BKO mice, but does not restore marginal zone B cells^[5].

Lysosomal Metabolism

GB111-NH2 (20-40 mg/kg; intraperitoneal injection; twice; 5 hours before and 48 hours after T-GNP injection) reduces cathepsin-dependent tumor accumulation and the CT signal of subsequently injected T-GNP-ABP in 4T1 tumor-bearing BALB/c mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

BALB/c (male, 3-4 weeks old)^[1]
Dosage:

40 mg/kg (5 h before T-GNP injection); 20 mg/kg (48 h after T-GNP injection)
Administration:

intraperitoneal; twice; 5 h before and 48 h after T-GNP injection
Result:

Resulted in lower tumor X-ray absorption/CT signal than T-GNP-ABP alone in 4T1 tumor-bearing mice.
Showed lower tumor signal by quantification of gold attenuation in CT scans and lower tumor gold accumulation by FAAS at 72 h.

Animal Model:

BALB/c (female, 4-5 weeks old)^[4]
Dosage:

40 mg/kg
Administration:

i.p.; once daily; for 3 days
Result:

Caused an increase in TAM caspase-3 activity by FACS.
The remaining tumor cell populations exhibited increased Nucview staining, indicating increased apoptosis throughout the tumor.
Primary tumor size measured externally on the mouse fat pad was reduced on day 4, and the tumor growth curve showed a decrease in tumor size in treated mice.
DCFDA signal specifically colocalized with F4/80 in TAMs of treated mice and not in the remaining cells of the tumor mass.
No increase in cell death was detected in circulating CD11b+ cells from the same treated mice.

Animal Model:

CD19-Cre/TSC1f/f (TSC1BKO)^[5]
Dosage:

1 mg/mouse in 10% DMSO, 15% Tween 80, 75% PBS
Administration:

intraperitoneal injection; two rounds of 3 days followed by 3 days of saline; one week
Result:

Efficiently blocked all cathepsin activity in the spleen in vivo, as assessed by ex vivo residual GB123 activity.
Analysis of marginal zone structure revealed intact MOMA-1 rings and intact MAdCAM1 structures in TSC1BKO mice.
LTα expression was elevated.
LTβR-positive cells appeared in the spleens of TSC1BKO mice.
Flow cytometry analyses did not detect regain of marginal zone B cells.
Marginal zone architecture was restored in a manner indistinguishable from normal mice.

Related Protocols :

Chemical Information

CAS No. 956479-18-8
Molecular Weight 573.68
Formula C₃₃H₃₉N₃O₆
SMILES

O=C(OCC([C@@H](NC([C@@H](NC(OCC1=CC=CC=C1)=O)CC2=CC=CC=C2)=O)CCCCN)=O)C3=C(C)C=CC=C3C
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Tsvirkun D, et al. CT Imaging of Enzymatic Activity in Cancer Using Covalent Probes Reveal a Size-Dependent Pattern. Journal of the American Chemical Society. 2018 Sep 26;140(38):12010-12020.

[2]. Hamed R, et al. Challenges in Batch-to-Bed Translation Involving Inflammation-Targeting Compounds in Chronic Epilepsy: The Case of Cathepsin Activity-Based Probes. ACS omega. 2024 Feb 13;9(6):6965-6975.

[3]. Withana NP, et al. Labeling of active proteases in fresh-frozen tissues by topical application of quenched activity-based probes. Nature protocols. 2016 Jan;11(1):184-91.

[4]. Salpeter SJ, et al. A novel cysteine cathepsin inhibitor yields macrophage cell death and mammary tumor regression. Oncogene. 2015 Dec 10;34(50):6066-78. [Content Brief]

[5]. Meena NK, et al. mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity. Immunology. 2018 Dec;155(4):505-518.

[6]. Abu-Fanne R, et al. α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol. The Journal of biological chemistry. 2016 Feb 05;291(6):2777-86.

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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GB111-NH2

All Cathepsin Isoforms

All TNF Receptor Isoforms