| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
GSK3α (IC50 = 327 nM) [1]
GSK3β (IC50 = 657 nM) [1] CDK9/cyclin T1 (IC50 = 321 nM) [1] |
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| ln Vitro |
Cell proliferation can be impacted by blocking cell cycle progression with ABC1183 (3 μM, 24 h) [1].
In a single-dose (10 μM) kinase screen against 414 human kinases, ABC1183 inhibited CDK9 (inactive), GSK3α, GSK3β, and CDK9/cyclin T1 by more than 60% [1]. - ABC1183 exhibited cytotoxicity against a panel of murine and human cancer cell lines with IC50 values ranging from 63 nM to 2.6 μM: LNCaP (63 nM), FaDu (130 nM), B-16 F10 (210 nM), Pan02 (220 nM), Mia-Paca2 (270 nM), BxPC3 (700 nM), SK-N-MC (2.6 μM) [1]. - Flow cytometry analysis showed that treatment with 3 μM ABC1183 for 24 hours in Pan02 cells significantly decreased the number of cells in G1 and S phases, and increased the number of cells in G2/M and sub-G1 phases [1]. - Western blot analysis demonstrated that ABC1183 treatment decreased GSK3α/β pSer21/9 in a time-dependent manner, with GSK3β more dramatically decreased than GSK3α. Cell-specific differences were observed: LNCaP cells showed transiently decreased GSK3β phosphorylation; FaDu cells showed rapid and persistent downregulation of GSK3β phosphorylation [1]. - ABC1183 decreased glycogen synthase (GS) phosphorylation at Ser641 in a cell-type-specific manner (LNCaP and FaDu cells at 24 hours) [1]. - ABC1183 increased β-catenin phosphorylation at Ser33/37/Thr41 (which targets the protein for proteasomal degradation) between 6 and 24 hours in all cell lines tested [1]. - ABC1183 decreased MCL1 total protein levels, most discernibly in LNCaP and Pan02 cells after 24 hours [1]. - ABC1183 decreased Pol2 activity measured by pSer5 Pol2, observable to similar levels as the CDK9 inhibitor flavopiridol [1]. - The CDK9-regulated gene Hexim1 was significantly decreased at the mRNA level following 24 hours of ABC1183 treatment [1]. |
| ln Vivo |
In male C57BL/6 mice, oral gavage of ABC1183 (5 or 50 mg/kg) suppresses tumor proliferation by downregulating pro-inflammatory signaling and cell growth [1].
In a B16 murine melanoma allograft model, oral administration of 5 mg/kg ABC1183 five times per week significantly suppressed tumor growth compared to vehicle [1]. - In TNBS-induced Crohn’s disease model, oral treatment with 50 mg/kg ABC1183 daily from day 6 to day 9 significantly reduced macroscopic inflammation scores in the distal colon compared to vehicle-treated TNBS group [1]. - In the same TNBS model, ABC1183 treatment reduced colonic TNF-α levels by 60% and IL-6 levels by 85% compared to vehicle-treated TNBS animals [1]. - In DSS-induced ulcerative colitis model, oral ABC1183 (50 mg/kg once daily) dramatically decreased Disease Activity Index (DAI) between days 4 and 6 compared to DSS/vehicle group [1]. - In the DSS model, ABC1183 treatment prevented colon shortening: colon lengths of ABC1183-treated mice were indistinguishable from controls, whereas DSS/vehicle mice had significantly shortened colons [1]. - In the DSS model, ABC1183 attenuated DSS-induced increase in myeloperoxidase (MPO) activity, indicating reduced neutrophil influx [1]. - In the DSS model, ABC1183 reversed IL-6 and IL-10 expression patterns (decreased IL-6, increased IL-10) but did not influence TNF-α levels [1]. |
| Enzyme Assay |
In vitro kinase selectivity screening: ABC1183 was screened at a single 10 μM concentration against a panel of 414 human kinases using ATP at Km(app). All kinases were tested in duplicate. Kinases showing greater than 60% inhibition were further subjected to dose-response IC50 determination assays [1].
- IC50 determination: Dose-response assays were carried out to calculate the IC50 values for GSK3α, GSK3β, and CDK9/cyclin T1. The IC50 for GSK3β was determined to be 657 nM, for GSK3α 327 nM, and for CDK9/cyclin T1 321 nM [1]. |
| Cell Assay |
Cell cycle analysis [1]
Cell Types: LNCaP human prostate cancer cells Tested Concentrations: 3 μM Incubation Duration: 24 hrs (hours) Experimental Results: G1 and S phase cells were Dramatically diminished, and G2/M and sub-G1 cycle cells were Dramatically increased. Sulforhodamine B assay for cell viability: Cells were seeded in 96-well plates. After 24 hours, they were treated with 0–100 μM ABC1183 for 72 hours. Cell viability was then determined using a standard sulforhodamine B assay [1]. - Flow cytometry for cell cycle analysis: Cells were treated and seeded under indicated conditions, then labeled with BrdU 2 hours before harvest. Cells were fixed in 100% ethanol, stained with FITC-conjugated anti-BrdU antibody, and processed using a flow cytometer [1]. - Western blot analysis: Cell lysates were prepared using a buffer containing Tris-HCl, NaCl, NP-40, sodium deoxycholate, and SDS. Total lysates were resolved by SDS-PAGE (10% or 4–12% gradient), transferred to PVDF membranes, and immunoblotted with antibodies against phospho-GSK3α/β (Ser21/9), GSK-3β, phospho-GS (Ser641), GS, phospho-β-catenin (Ser33/37/Thr41), β-catenin, MCL1, and HRP-GAPDH [1]. - Cellular thermal shift assay (CETSA): To determine physical engagement of ABC1183 with target proteins, cells were treated with ABC1183 or DMSO for indicated times, then trypsinized. Half of the cells were resuspended in PBS with protease inhibitors and heated at 55°C for 3 minutes (the lowest thermal point for GSK3α/β protein degradation identified from preliminary experiments); the other half was not heated as a loading control. Protein bound by ABC1183 is protected from thermal degradation [1]. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice infected with Crohn's disease [1]
Doses: 50 mg/kg Route of Administration: po (oral gavage); daily; 3 days Experimental Results: TNF-α diminished by 65%, IL-6 diminished by 30 %, IL-1β diminished by 45%. Animal/Disease Models: Ulcerative colitis male C57BL/6 mice [1] Doses: 50 mg/kg Route of Administration: po (oral gavage); one time/day; 6 days Experimental Results: The expression of anti-inflammatory factor IL-10 increased, while pro-inflammatory Expression of factor IL-6 is diminished. Tumor model (B16 melanoma): Seven-week-old male C57BL/6 mice were subcutaneously injected with tumor cells in the flank in 100 μl PBS or PBS/Geltrex. When tumors reached approximately 100–150 mm³, mice were administered 5 mg/kg ABC1183 or vehicle (50% PEG400, 35% propanediol, 5% Tween 80, 5% EtOH, 5% saline) by oral gavage five times per week. Body weight was monitored throughout, and tumor volume was measured with calipers [1]. - TNBS-induced Crohn’s disease model: Male C57BL/6 mice were anesthetized, and a 0.1 ml solution of 50 μg/g TNBS in 50% ethanol/PBS was slowly administered rectally via a stainless steel catheter inserted 4 cm proximal to the anus. Mice were inverted for 30 minutes to ensure retention. Colitis was induced by TNBS delivery on experimental days 0 and 7. Starting on day 6 through day 9, animals were treated daily by oral gavage with either vehicle or 50 mg/kg ABC1183. On day 10, animals were sacrificed, colons were removed, measured, weighed, and the distal 3 cm was scored for macroscopic inflammation [1]. - DSS-induced ulcerative colitis model: Male C57BL/6 mice were divided into groups: vehicle-only, DSS (40,000 mol. wt.) plus vehicle, or DSS plus ABC1183 (50 mg/kg). DSS was administered as a 2% solution continuously in drinking water. Vehicle or ABC1183 was administered once daily by oral gavage in a volume of 0.1 ml per dose. Disease Activity Index (monitoring weight loss, stool consistency, and blood in stool) was scored on days 4–6. Mucosal myeloperoxidase (MPO) activity was determined by assaying the middle one-third of the colon, quantifying the metabolism of tetramethylbenzidine [1]. |
| Toxicity/Toxicokinetics |
In a 7-day toxicity study, ABC1183 was administered by oral gavage daily for 7 days at indicated doses. After sacrifice, hematology, blood chemistry, and organ weight analyses showed no organ or hematologic toxicity [1].
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| References | |
| Additional Infomation |
ABC1183 is a novel diaminothiazole compound designed as a selective GSK3α/β and CDK9 inhibitor. It is orally available [1].
- ABC1183 is an ATP-competitive inhibitor for both GSK3 isoforms but a noncompetitive ATP inhibitor for CDK9/cyclin T1 [1]. - Within 15 minutes of incubation, ABC1183 physically associates with GSK3α and GSK3β, protecting them from thermal degradation in CETSA [1]. - ABC1183 treatment decreases cell survival through G2/M arrest and modulates oncogenic signaling through changes in GSK3, glycogen synthase, and β-catenin phosphorylation and MCL1 expression [1]. - The compound suppresses tumor growth and inflammation-driven gastrointestinal disease symptoms, owing in part to downregulation of TNF-α and IL-6 proinflammatory cytokines [1]. |
| Molecular Formula |
C18H14N4OS
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|---|---|
| Molecular Weight |
334.394961833954
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| Exact Mass |
334.088
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| CAS # |
1042735-18-1
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| PubChem CID |
134500787
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
489
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(=NC(=C1C(C1C=CC(C#N)=CC=1)=O)N)NC1C=CC(C)=CC=1
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| InChi Key |
CUDLEXBIVZPJBU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14N4OS/c1-11-2-8-14(9-3-11)21-18-22-17(20)16(24-18)15(23)13-6-4-12(10-19)5-7-13/h2-9H,20H2,1H3,(H,21,22)
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| Chemical Name |
4-(4-Amino-2-p-tolylamino-thiazole-5-carbonyl)-benzonitrile
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| Synonyms |
ABC-1183 ABC 1183 ABC1183
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~373.82 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9904 mL | 14.9522 mL | 29.9043 mL | |
| 5 mM | 0.5981 mL | 2.9904 mL | 5.9809 mL | |
| 10 mM | 0.2990 mL | 1.4952 mL | 2.9904 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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