TH588 | CAS#1609960-31-7 | MTH1 (NUDT1) inhibitor

MedKoo Cat#: 406659 | Name: TH588

Description:

WARNING: This product is for research use only, not for human or veterinary use.

TH588 is a potent inhibitor of human 7,8-Dihydro-8-oxoguaninetriphosphatase MTH1 (NUDT1) with an IC50 value of 5 nM and good metabolic stability. Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. TH588 a first-in-class nudix hydrolase family inhibitor that potently and selectively engages and inhibits the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitor binds in the active site of MTH1.

Chemical Structure

TH588

CAS#1609960-31-7 (free base)

Theoretical Analysis

MedKoo Cat#: 406659

Name: TH588

CAS#: 1609960-31-7 (free base)

Chemical Formula: C13H12Cl2N4

Exact Mass: 294.0439

Molecular Weight: 295.17

Elemental Analysis: C, 52.90; H, 4.10; Cl, 24.02; N, 18.98

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to Ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
1g	USD 4,250.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

1609960-31-7 (free base) 1640282-30-9 (HCl)

Synonym

TH588; TH-588; TH 588.

IUPAC/Chemical Name

N4-cyclopropyl-6-(2,3-dichlorophenyl)pyrimidine-2,4-diamine

InChi Key

PNMYJIOQIAEYQL-UHFFFAOYSA-N

InChi Code

InChI=1S/C13H12Cl2N4/c14-9-3-1-2-8(12(9)15)10-6-11(17-7-4-5-7)19-13(16)18-10/h1-3,6-7H,4-5H2,(H3,16,17,18,19)

SMILES Code

NC1=NC(C2=CC=CC(Cl)=C2Cl)=CC(NC3CC3)=N1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Certificate of Analysis

View CoA: current batch, Lot#CRB51228

QC Data

View QC data: current batch, Lot#CRB51228

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 295.17 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

1: Ren C, Shi Z, Zhang X, Yu X, Gao Y, Qi Z, Chen Y, Wang Y. DNA-mediated self- assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy. Bioact Mater. 2024 Dec 3;45:434-445. doi: 10.1016/j.bioactmat.2024.11.009. PMID: 39697239; PMCID: PMC11653152. 2: Zhang W, Ran Y, Yang M, Hu Y, Wang Z, Cao Y, Ran H. An Oxidative Stress Nano- Amplifier for Improved Tumor Elimination and Combined Immunotherapy. Adv Healthc Mater. 2024 Dec;13(31):e2402349. doi: 10.1002/adhm.202402349. Epub 2024 Sep 2. PMID: 39221686. 3: Shao Y, Chen M, Chen W, Wang Z, Sui M, Tian M, Wu Y, Song J, Ji D, Song F. Integration of Activation by Hypoxia and Inhibition Resistance of Tumor Cells to Apoptosis for Precise and Augmented Photodynamic Therapy. Adv Healthc Mater. 2023 Oct;12(25):e2300503. doi: 10.1002/adhm.202300503. Epub 2023 Jun 25. PMID: 37306493. 4: Song Q, Zhang Y, Deng X, Zhao H, Zhang Y, Li J, Chen W, Hu H, Zhang Y. Amplification of oxidative stress with a hyperthermia-enhanced chemodynamic process and MTH1 inhibition for sequential tumor nanocatalytic therapy. J Mater Chem B. 2023 May 3;11(17):3836-3850. doi: 10.1039/d2tb02673b. PMID: 36976579. 5: Henriksson S, Calderón-Montaño JM, Solvie D, Warpman Berglund U, Helleday T. Overexpressed c-Myc Sensitizes Cells to TH1579, a Mitotic Arrest and Oxidative DNA Damage Inducer. Biomolecules. 2022 Nov 29;12(12):1777. doi: 10.3390/biom12121777. PMID: 36551206; PMCID: PMC9775511. 6: Song Q, Yang W, Deng X, Zhang Y, Li J, Xing X, Chen W, Liu W, Hu H, Zhang Y. Platinum-based nanocomposites loaded with MTH1 inhibitor amplify oxidative damage for cancer therapy. Colloids Surf B Biointerfaces. 2022 Oct;218:112715. doi: 10.1016/j.colsurfb.2022.112715. Epub 2022 Aug 2. PMID: 35932557. 7: Rajendraprasad G, Eibes S, Boldú CG, Barisic M. TH588 and Low-Dose Nocodazole Impair Chromosome Congression by Suppressing Microtubule Turnover within the Mitotic Spindle. Cancers (Basel). 2021 Nov 29;13(23):5995. doi: 10.3390/cancers13235995. PMID: 34885104; PMCID: PMC8657032. 8: Li XY, Deng FA, Zheng RR, Liu LS, Liu YB, Kong RJ, Chen AL, Yu XY, Li SY, Cheng H. Carrier Free Photodynamic Synergists for Oxidative Damage Amplified Tumor Therapy. Small. 2021 Oct;17(40):e2102470. doi: 10.1002/smll.202102470. Epub 2021 Sep 4. PMID: 34480417. 9: Oksvold MP, Berglund UW, Gad H, Bai B, Stokke T, Rein ID, Pham T, Sanjiv K, Øy GF, Norum JH, Smeland EB, Myklebust JH, Helleday T, Våtsveen TK. Karonudib has potent anti-tumor effects in preclinical models of B-cell lymphoma. Sci Rep. 2021 Mar 18;11(1):6317. doi: 10.1038/s41598-021-85613-8. PMID: 33737576; PMCID: PMC7973795. 10: Wang X, Wu Y, Zhang L, Li YX, Han B, Shi X, Wang W, Wang LS. [Proliferation- Inhibitory and Apoptosis-Inducing Effects of Targeting MTH1 on Multiple Myeloma Cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Oct;28(5):1598-1604. Chinese. doi: 10.19746/j.cnki.issn.1009-2137.2020.05.028. PMID: 33067960. 11: Alnajjar K, Sweasy JB. Timing Is Everything: Misincorporation of 8oxodG during Mitosis Is Lethal. Cancer Res. 2020 Sep 1;80(17):3459-3460. doi: 10.1158/0008-5472.CAN-20-1904. PMID: 32878864. 12: Chen Z, Chen C, Zhou T, Duan C, Wang Q, Zhou X, Zhang X, Wu F, Hua Y, Lin F. A high-throughput drug combination screen identifies an anti-glioma synergism between TH588 and PI3K inhibitors. Cancer Cell Int. 2020 Jul 23;20:337. doi: 10.1186/s12935-020-01427-0. PMID: 32714096; PMCID: PMC7376673. 13: Rudd SG, Gad H, Sanjiv K, Amaral N, Hagenkort A, Groth P, Ström CE, Mortusewicz O, Berglund UW, Helleday T. MTH1 Inhibitor TH588 Disturbs Mitotic Progression and Induces Mitosis-Dependent Accumulation of Genomic 8-oxodG. Cancer Res. 2020 Sep 1;80(17):3530-3541. doi: 10.1158/0008-5472.CAN-19-0883. Epub 2020 Apr 20. PMID: 32312836. 14: Zhao L, Li J, Su Y, Yang L, Chen L, Qiang L, Wang Y, Xiang H, Tham HP, Peng J, Zhao Y. MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy. Sci Adv. 2020 Mar 4;6(10):eaaz0575. doi: 10.1126/sciadv.aaz0575. PMID: 32181355; PMCID: PMC7056313. 15: Moukengue B, Brown HK, Charrier C, Battaglia S, Baud'huin M, Quillard T, Pham TM, Pateras IS, Gorgoulis VG, Helleday T, Heymann D, Berglund UW, Ory B, Lamoureux F. TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model. EBioMedicine. 2020 Mar;53:102704. doi: 10.1016/j.ebiom.2020.102704. Epub 2020 Mar 7. PMID: 32151797; PMCID: PMC7063190. 16: Samaranayake GJ, Troccoli CI, Zhang L, Huynh M, Jayaraj CJ, Ji D, McPherson L, Onishi Y, Nguyen DM, Robbins DJ, Karbaschi M, Cooke MS, Barrientos A, Kool ET, Rai P. The Existence of MTH1-independent 8-oxodGTPase Activity in Cancer Cells as a Compensatory Mechanism against On-target Effects of MTH1 Inhibitors. Mol Cancer Ther. 2020 Feb;19(2):432-446. doi: 10.1158/1535-7163.MCT-19-0437. Epub 2019 Nov 19. PMID: 31744893; PMCID: PMC7079300. 17: Gul N, Karlsson J, Tängemo C, Linsefors S, Tuyizere S, Perkins R, Ala C, Zou Z, Larsson E, Bergö MO, Lindahl P. The MTH1 inhibitor TH588 is a microtubule- modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway. Sci Rep. 2019 Oct 11;9(1):14667. doi: 10.1038/s41598-019-51205-w. PMID: 31604991; PMCID: PMC6789014. 18: Wang J, Nagy N, Masucci MG. The Epstein-Barr virus nuclear antigen-1 upregulates the cellular antioxidant defense to enable B-cell growth transformation and immortalization. Oncogene. 2020 Jan;39(3):603-616. doi: 10.1038/s41388-019-1003-3. Epub 2019 Sep 11. Erratum in: Oncogene. 2020 Feb;39(9):2028. doi: 10.1038/s41388-019-1066-1. PMID: 31511648; PMCID: PMC6962091. 19: Lee JW, Lee S, Ho JN, Youn JI, Byun SS, Lee E. Antitumor effects of MutT homolog 1 inhibitors in human bladder cancer cells. Biosci Biotechnol Biochem. 2019 Dec;83(12):2265-2271. doi: 10.1080/09168451.2019.1648207. Epub 2019 Jul 31. PMID: 31362565. 20: Patterson JC, Joughin BA, Prota AE, Mühlethaler T, Jonas OH, Whitman MA, Varmeh S, Chen S, Balk SP, Steinmetz MO, Lauffenburger DA, Yaffe MB. VISAGE Reveals a Targetable Mitotic Spindle Vulnerability in Cancer Cells. Cell Syst. 2019 Jul 24;9(1):74-92.e8. doi: 10.1016/j.cels.2019.05.009. Epub 2019 Jul 10. PMID: 31302152; PMCID: PMC6688637.