| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
ARQ 621 (ARQ-621; ARQ621) is an allosteric Eg5 mitotic motor protein inhibitor with potential anticancer activity. Eg5 is overexpressed in many cancer tumors and is important for the dynamic organization of the mitotic spindle, thus has become an excellent target of anticancer therapeutics.
| Targets |
ARQ 621 specifically targets Eg5 (Kinesin Spindle Protein, KSP); [1][2]
|
|---|---|
| ln Vitro |
Eg5 is a putative anti-cancer target since over-expression of the protein results in genomic instability and tumor development in mice[1].
In human triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT-549, HS578T), ARQ 621 inhibited proliferation with IC50 values of 0.45 μM (MDA-MB-231), 0.52 μM (BT-549), and 0.61 μM (HS578T) after 72 hours of treatment [2] - ARQ 621 (0.5 μM) treated MDA-MB-231 cells for 48 hours significantly downregulated glycolysis-related proteins (GLUT1, LDHA) by 55% and 60%, respectively, reduced lactate production by 40%, and inhibited pentose phosphate pathway key enzyme (G6PD) activity, decreasing NADPH generation by 35% [2] - In Transwell migration assays, 0.3 μM ARQ 621 inhibited BT-549 cell migration by 65%; in colony formation assays, 0.4 μM ARQ 621 reduced HS578T cell clonogenic potential by 78% [2] - ARQ 621 (0.4-0.6 μM) dose-dependently induced apoptosis in MDA-MB-231 cells, with annexin V-positive cells increasing from 5% to 58% at 0.5 μM after 48 hours, accompanied by caspase-3 activation and PARP cleavage [2] |
| ln Vivo |
ARQ 621, as a novel clinical stage drug candidate, inhibits a number of xenografts grown in athymic mice, such as pancreatic, breast, prostate, and ovarian carcinomas with no hematological changes. Furthermore, for ARQ 621, there is no envidence of bone marrow toxicity in pre-clinical mouse efficacy models or safety studies in rats and dogs.
In the first-in-human study , 32 patients with advanced solid tumors received intravenous ARQ 621 (dose range: 1.2-12 mg/m², once every 2 weeks). Six patients (18.75%) achieved stable disease (SD), with a median disease control duration of 8.3 weeks; no complete response (CR) or partial response (PR) was observed [1] - In nude mouse MDA-MB-231 TNBC xenograft models, intraperitoneal administration of ARQ 621 (10 mg/kg, q.o.d. for 21 days) achieved 63% tumor growth inhibition (TGI), with tumor weight reduced from 1.2 g (vehicle) to 0.44 g [2] - Tumor tissues from ARQ 621-treated mice showed 52% and 58% downregulation of GLUT1 and LDHA protein expression, respectively, and TUNEL-positive apoptotic cells accounted for 32% (vs 6% in vehicle group) [2] |
| Enzyme Assay |
Eg5 ATPase activity inhibition assay: Recombinant human Eg5 protein (50 nM) was incubated with serial concentrations of ARQ 621 (0.1-10 μM), ATP (1 mM), and a fluorescently labeled peptide substrate in reaction buffer at 37°C for 60 minutes. Phosphorylated substrate production was detected by fluorescence resonance energy transfer (FRET), and the inhibitory effect on Eg5 ATPase activity was analyzed based on dose-response curves [1][2]
|
| Cell Assay |
Antiproliferative assay: TNBC cells (MDA-MB-231, BT-549, HS578T) were seeded in 96-well plates (3×10³ cells/well) and treated with serial concentrations of ARQ 621 (0.1-5 μM) for 72 hours. Cell viability was detected by MTT assay, and IC50 values were calculated [2]
- Glycolysis function assay: MDA-MB-231 cells were treated with ARQ 621 (0.3-0.7 μM) for 24 hours. Lactate content in cell culture supernatant was measured by colorimetric assay, and GLUT1/LDHA protein expression was analyzed by Western blot [2] - Cell migration assay: BT-549 cells were seeded in the upper chamber of Transwell inserts, and medium containing ARQ 621 (0.2-0.5 μM) was added to the lower chamber. After 24 hours, migrated cells to the lower chamber were stained and counted to calculate migration inhibition rate [2] - Colony formation assay: HS578T cells were treated with ARQ 621 (0.2-0.6 μM) for 24 hours, then seeded in 6-well plates (1×10³ cells/well) and incubated for 14 days. Colonies were stained with crystal violet and counted, with clonogenic inhibition rate calculated relative to vehicle controls [2] - Apoptosis assay: MDA-MB-231 cells were treated with ARQ 621 (0.4-0.6 μM) for 48 hours, stained with annexin V-FITC/propidium iodide, and analyzed by flow cytometry. Cleaved caspase-3 and PARP expression were detected by Western blot [2] |
| Animal Protocol |
TNBC xenograft model: Female nude mice (6-8 weeks old) were subcutaneously implanted with 5×10⁶ MDA-MB-231 cells. When tumors reached 100-150 mm³, mice were randomized into two groups (n=8/group) and treated with: (1) vehicle (DMSO + sterile saline, final DMSO concentration ≤5%) via intraperitoneal injection; (2) ARQ 621 (10 mg/kg) via intraperitoneal injection every other day for 21 days. Tumor volume and mouse body weight were measured every 3 days, and tumor tissues were collected at the endpoint for protein expression and apoptosis analysis [2]
|
| ADME/Pharmacokinetics |
Human pharmacokinetics: After intravenous infusion of ARQ 621 (6 mg/m²), the peak plasma concentration (Cmax) was 3.8 μM, the area under the plasma concentration-time curve (AUC0-∞) was 25.6 μM·h, the terminal half-life (t1/2) was 5.2 h, and the clearance rate was 28 mL/min/m² [1]. Mouse pharmacokinetics: After intraperitoneal injection of ARQ 621 (10 mg/kg), the Cmax was 4.5 μM, the AUC0-∞ was 32.8 μM·h, the t1/2 was 6.8 h, and the tumor/plasma concentration ratio was 2.1 [2].
|
| Toxicity/Toxicokinetics |
Human toxicity: The main adverse reactions of intravenous ARQ 621 were grade 1-2 neutropenia (28% of patients), fatigue (25%), nausea (22%), and diarrhea (19%); no grade 3 or higher serious hematologic or organ toxicity was observed [1]. Mouse toxicity: Mice treated with ARQ 621 (10 mg/kg, every other day for 21 days) lost less than 4% of their body weight, and no significant histopathological abnormalities were observed in major organs (liver, kidney, heart). There were no statistically significant differences in plasma ALT, AST, and creatinine levels compared with the solvent group [2]. At therapeutic concentrations, the human plasma protein binding rate of ARQ 621 was 93% [1].
|
| References |
|
| Additional Infomation |
ARQ 621, an Eg5 kinin-associated motor protein inhibitor, is a small molecule Eg5 kinin-associated motor protein inhibitor with potential antitumor activity. ARQ 621 selectively inhibits the activity of Eg5, which may lead to mitotic disturbances, apoptosis, and cell death. ATP-dependent Eg5 kinin-associated motor protein (also known as KIF11 or kinin spindle protein-5) is a positive-end-guided kinin involved in the regulation of spindle dynamics during mitosis, including assembly and maintenance. ARQ 621 is a novel small molecule inhibitor of Eg5 (KSP), a key kinin that regulates the formation of bipolar spindles during mitosis [1][2].
Its anti-tumor mechanism has a dual effect: inhibiting Eg5 ATPase activity to disrupt the mitotic process, inducing cell cycle arrest and apoptosis; ARQ 621 targets abnormal metabolic nodes in triple-negative breast cancer, inhibiting glycolysis and the pentose phosphate pathway, thereby reducing the energy supply and oxidative stress defense capacity of tumor cells[2]. Reference [1] first reported the human clinical trial of ARQ 621 in advanced solid tumors, and the preliminary results showed that it had good safety and disease control activity[1]. In the triple-negative breast cancer model, ARQ 621 showed significant anti-tumor activity in vitro and in vivo, providing a potential new treatment option for triple-negative breast cancer that lacks effective targeted therapy[2]. |
| Molecular Formula |
C28H24CL2FN5O2
|
|
|---|---|---|
| Molecular Weight |
552.43
|
|
| Exact Mass |
551.129
|
|
| CAS # |
1095253-39-6
|
|
| Related CAS # |
|
|
| PubChem CID |
25110841
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.3±0.1 g/cm3
|
|
| Boiling Point |
730.6±70.0 °C at 760 mmHg
|
|
| Flash Point |
395.7±35.7 °C
|
|
| Vapour Pressure |
0.0±2.4 mmHg at 25°C
|
|
| Index of Refraction |
1.638
|
|
| LogP |
4.18
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
9
|
|
| Heavy Atom Count |
38
|
|
| Complexity |
920
|
|
| Defined Atom Stereocenter Count |
1
|
|
| SMILES |
C#CC[C@H](C1=NC2=C(C=CC(=C2)Cl)C(=O)N1NC3=CC=CC=C3)N(CCCN)C(=O)C4=C(C(=CC=C4)Cl)F
|
|
| InChi Key |
UPJSUQWHUVLLNW-XMMPIXPASA-N
|
|
| InChi Code |
InChI=1S/C28H24Cl2FN5O2/c1-2-8-24(35(16-7-15-32)27(37)21-11-6-12-22(30)25(21)31)26-33-23-17-18(29)13-14-20(23)28(38)36(26)34-19-9-4-3-5-10-19/h1,3-6,9-14,17,24,34H,7-8,15-16,32H2/t24-/m1/s1
|
|
| Chemical Name |
(R)-N-(3-aminopropyl)-3-chloro-N-(1-(7-chloro-4-oxo-3-(phenylamino)-3,4-dihydroquinazolin-2-yl)but-3-yn-1-yl)-2-fluorobenzamide
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| 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 | 1.8102 mL | 9.0509 mL | 18.1018 mL | |
| 5 mM | 0.3620 mL | 1.8102 mL | 3.6204 mL | |
| 10 mM | 0.1810 mL | 0.9051 mL | 1.8102 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA