TAS4464 hydrochloride

Name: TAS4464 hydrochloride
Brand: MedChemExpress
SKU: HY-128586A
Rating: 5.0 (9 reviews)

Cat. No.: HY-128586A Purity: 98.91%: Data Sheet
COA

SDS
Handling Instructions
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TAS4464 hydrochloride is a long-acting, highly selective covalent inhibitor targeting NEDD8-activating enzyme (NAE) (IC₅₀=0.955 nM), and also inhibits CAII with an IC₅₀ of 0.73 μM, which is less potent than MLN4924 (HY-70062). The IC₅₀ values of TAS4464 hydrochloride against other E1 enzymes UAE and SAE are 449 nM and 1280 nM, respectively. TAS4464 hydrochloride targets NEDD8 in an ATP-dependent manner to inhibit NAE, blocks the neddylation pathway, causes accumulation of CRL ubiquitin ligase substrates (such as CDT1, p27, phosphorylated IκBα), and further induces tumor cell apoptosis. TAS4464 hydrochloride exhibits antiproliferative and cytotoxic effects, and has broad-spectrum antitumor activity against various hematologic and solid tumor cell lines as well as patient-derived tumor cells. TAS4464 hydrochloride has a wide therapeutic window, without obvious toxicity. TAS4464 hydrochloride can be used in the research of hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.) and solid tumors (small cell lung cancer, colorectal cancer, sarcoma, endometrial cancer, ovarian cancer, etc.).

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

TAS4464 hydrochloride Chemical Structure

CAS No. : 1848959-11-4

Size	Stock	Quantity

Free Sample (0.1 - 0.2 mg)	Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
200 mg	Get quote
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Customer Review

Based on 9 publication(s) in Google Scholar

Other Forms of TAS4464 hydrochloride:

TAS4464 In-stock

9 Publications Citing Use of MCE TAS4464 hydrochloride

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•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Carbonic Anhydrase Isoform Specific Products:

View All Isoforms

CA CA I CA Ⅱ CA IX CA XII CA VII CA VI CA VA CA VB CA XIII CA XIV

Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

CA Ⅱ

0.73 μM (IC₅₀)

In Vitro

TAS4464 hydrochloride is a highly potent and selective recombinant NAE inhibitor, with over 470-fold and 1340-fold selectivity against recombinant UAE and SAE, respectively, and weak off-target inhibitory activity against CA2^[1].
TAS4464 hydrochloride (1-10 μM; 24-48 h) induces apoptosis in leukemia, lymphoma, multiple myeloma and solid tumor cell lines, with the apoptosis rate increasing as the drug concentration rises^[1].
TAS4464 hydrochloride (1 nM-1 μM, 4 h; 100 nM, 1-24 h) significantly increases the protein expression levels of CRL ubiquitin ligase substrates CDT1, p27, and phosphorylated IκBα in tumor cells, while reduces the level of cullin neddylation modification^[1].
TAS4464 hydrochloride (0.1-10 μM; 24-48 h) significantly inhibits the migratory capacity of solid tumor cell lines such as colorectal cancer and sarcoma, with a concentration-dependent inhibitory effect^[1].

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

Cell Viability Assay^[1]

Cell Line:	Multiple hematologic malignancy cell lines (leukemia, lymphoma, multiple myeloma) and solid tumor cell lines (small cell lung cancer, colorectal cancer, sarcoma, endometrial cancer, ovarian cancer)
Concentration:	0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM
Incubation Time:	24 h, 48 h, 72 h
Result:	Significantly inhibited the cell viability of various hematologic malignancy and solid tumor cell lines in a concentration- and time-dependent manner.

Western Blot Analysis^[1]

Cell Line:	Multiple tumor cell lines (hematologic and solid tumor)
Concentration:	1 nM, 10 nM, 100 nM, 1 μM, 10 μM
Incubation Time:	6 h, 12 h, 24 h, 48 h
Result:	Significantly increased the protein expression levels of CRL ubiquitin ligase substrates (CDT1, p27, phosphorylated IκBα) in tumor cells, and decreased the level of cullin neddylation modification.

In Vivo

TAS4464 (25-100 mg/kg; i.v.; twice weekly; 3 weeks) hydrochloride achieves complete tumor regression and induces apoptosis in models of T-cell acute lymphoblastic leukemia (25 mg/kg), mantle cell lymphoma (100 mg/kg), clear cell sarcoma (100 mg/kg), and small cell lung cancer (75 mg/kg), with a broad therapeutic window^[1].
TAS4464 (100 mg/kg; i.v.; administered on days 1, 4, 8 and 11, with one cycle every 21 days; 8 cycles total) hydrochloride significantly prolongs survival and reduces tumor burden in a systemic diffuse large B-cell lymphoma model of SCID mice xenografted with TMD8-Luc^[1].

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

Animal Model:	BALB/cAJcl-nu/nu (6-week-old male; subcutaneously implanted with CCRF-CEM cells)^[1]
Dosage:	6.3 mg/kg; 12.5 mg/kg; 25 mg/kg; 50 mg/kg; 100 mg/kg
Administration:	i.v.; weekly; 3 weeks
Result:	Reduced mean tumor volume significantly compared to vehicle control (P < 0.05). Achieved T/C ratios of 35%, 20%, 10%, 1%, and 0% for 6.3, 12.5, 25, 50, and 100 mg/kg, respectively. Induced complete tumor regression at doses of 25, 50, and 100 mg/kg. Decreased cullin1 neddylation, increased accumulation of CRL substrates CDT1, NRF2, and p-IκBα, and elevated levels of cleaved caspase-3 and cleaved PARP within 24 hours of administration. Showed stronger, more durable reduction of NEDD8-cullin1 signal with increasing doses, with longer-lasting inhibition than MLN4924. Caused no marked body weight loss.

Animal Model:	C.B-17 SCID (6-week-old male; subcutaneously implanted with GRANTA-519 cells)^[1]
Dosage:	100 mg/kg
Administration:	i.v.; weekly; 3 weeks; i.v.; twice weekly; 3 weeks
Result:	Exerted statistically significant antitumor activity vs vehicle control at day 22 (P < 0.05). Exceeded the antitumor activity of bortezomib and ibrutinib (P < 0.05). Induced massive apoptosis in tumor tissue. Caused no body weight loss exceeding 10% of initial weight.

Animal Model:	BALB/cAJcl-nu/nu (6-week-old male; subcutaneously implanted with SU-CCS-1 cells)^[1]
Dosage:	100 mg/kg
Administration:	i.v.; weekly; 3 weeks
Result:	Exerted statistically significant antitumor activity vs vehicle control (P < 0.05), with marked tumor regression maintained throughout treatment. Showed superior efficacy to doxorubicin hydrochloride, pazopanib, and MLN4924 (P < 0.05). Induced cleaved PARP (apoptotic marker) within 4 hours post-administration, and large necrotic tumor areas by day 3. Caused no body weight loss exceeding 10% of initial weight.

Animal Model:	NOD-SCID (6-week-old female; subcutaneously implanted with LU5266 patient-derived cells)^[1]
Dosage:	75 mg/kg
Administration:	i.v.; weekly; 3 weeks; i.v.; twice weekly; 3 weeks
Result:	Exerted statistically significant antitumor activity vs vehicle control, with a majority of mice achieving complete tumor regression in both treatment groups. Maintained tumor growth inhibition beyond 7 weeks. Showed superior efficacy to cisplatin and etoposide (P < 0.05). Caused no body weight loss exceeding 10% of initial weight.

Animal Model:	SCID (6-week-old; systemically implanted via tail vein with 1×10⁷ TMD8-Luc luciferase-expressing cells; treatment initiated 11 days post-transplantation)^[1]
Dosage:	100 mg/kg
Administration:	i.v.; on days 1, 4, 8, 11 of each 21-day cycle; 8 cycles
Result:	Prolonged survival time significantly compared to vehicle control, with median survival time>159 days and an increase in life span of 174%. Reduced mean relative photon value (tumor burden index) significantly compared to vehicle control.

Molecular Weight

542.97

Formula

C₂₁H₂₄ClFN₆O₆S

CAS No.

1848959-11-4

Appearance

Solid

Color

Light yellow to khaki

SMILES

NC1=NC=NC2=C1C(C#CC3=C(F)C=CC=C3OCC)=CN2[C@@H]4O[C@H](CNS(=O)(N)=O)[C@@H](O)[C@H]4O.Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (184.17 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : 5 mg/mL (9.21 mM; ultrasonic and warming and heat to 60°C)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.8417 mL	9.2086 mL	18.4172 mL
5 mM	0.3683 mL	1.8417 mL	3.6834 mL
10 mM	0.1842 mL	0.9209 mL	1.8417 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (3.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (3.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (3.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 98.91%

Select Batch:

Data Sheet (292 KB) SDS (393 KB)

COA (261 KB) LCMS (94 KB)

Handling Instructions (2659 KB)

References

[1]. Yoshimura C, et al. TAS4464, a highly potent and selective inhibitor of NEDD8-activating enzyme, suppresses neddylation and shows antitumor activity in diverse cancer models[J]. Molecular Cancer Therapeutics, 2019, 18(7): 1205-1216.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

H₂O / DMSO	1 mM	1.8417 mL	9.2086 mL	18.4172 mL	46.0431 mL
H₂O / DMSO	5 mM	0.3683 mL	1.8417 mL	3.6834 mL	9.2086 mL
DMSO	10 mM	0.1842 mL	0.9209 mL	1.8417 mL	4.6043 mL
	15 mM	0.1228 mL	0.6139 mL	1.2278 mL	3.0695 mL
	20 mM	0.0921 mL	0.4604 mL	0.9209 mL	2.3022 mL
	25 mM	0.0737 mL	0.3683 mL	0.7367 mL	1.8417 mL
	30 mM	0.0614 mL	0.3070 mL	0.6139 mL	1.5348 mL
	40 mM	0.0460 mL	0.2302 mL	0.4604 mL	1.1511 mL
	50 mM	0.0368 mL	0.1842 mL	0.3683 mL	0.9209 mL
	60 mM	0.0307 mL	0.1535 mL	0.3070 mL	0.7674 mL
	80 mM	0.0230 mL	0.1151 mL	0.2302 mL	0.5755 mL
	100 mM	0.0184 mL	0.0921 mL	0.1842 mL	0.4604 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.