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MedKoo Cat#: 406660 | Name: TH287
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Description:

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

TH287 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. TH287 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

TH287
TH287
CAS#1609960-30-6

Theoretical Analysis

MedKoo Cat#: 406660

Name: TH287

CAS#: 1609960-30-6

Chemical Formula: C11H10Cl2N4

Exact Mass: 268.0283

Molecular Weight: 269.13

Elemental Analysis: C, 49.09; H, 3.75; Cl, 26.34; N, 20.82

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 weeks
100mg USD 750.00 2 weeks
200mg USD 1,250.00 2 weeks
500mg USD 2,650.00 2 weeks
1g USD 4,250.00 2 weeks
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Related CAS #
No Data
Synonym
TH287; TH 287; TH-287.
IUPAC/Chemical Name
6-(2,3-dichlorophenyl)-N4-methylpyrimidine-2,4-diamine
InChi Key
URWCXPXBBITYLR-UHFFFAOYSA-N
InChi Code
InChI=1S/C11H10Cl2N4/c1-15-9-5-8(16-11(14)17-9)6-3-2-4-7(12)10(6)13/h2-5H,1H3,(H3,14,15,16,17)
SMILES Code
NC1=NC(C2=CC=CC(Cl)=C2Cl)=CC(NC)=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
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Preparing Stock Solutions

The following data is based on the product molecular weight 269.13 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.

Recalculate based on batch purity %
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: Zhu H, Cui M, Tang Q, Zhao H, Zhang P, Zeng S, Li W, Zhou Q, Zhang J, Chen Y. Photoactivated full-API nanodrug (FAND): harnessing transition metal complexes and MTH1 inhibitor for enhanced DNA damage in cancer cells. Biomater Sci. 2024 Jun 11;12(12):3154-3162. doi: 10.1039/d4bm00316k. PMID: 38687170. 2: Chen G, Wang X, He Z, Li X, Yang Z, Zhang Y, Li Y, Zheng L, Miao Y, Zhang D. Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy. Molecules. 2023 May 28;28(11):4397. doi: 10.3390/molecules28114397. PMID: 37298873; PMCID: PMC10254276. 3: Wang X, Song K, Fan Y, Du J, Liu J, Xu J, Zheng L, Ouyang R, Li Y, Miao Y, Zhang D. Ultrasound-triggered reactive oxygen species effector nanoamplifier for enhanced combination therapy of mutant p53 tumors. Colloids Surf B Biointerfaces. 2022 Jul;215:112489. doi: 10.1016/j.colsurfb.2022.112489. Epub 2022 Apr 4. PMID: 35395477. 4: Hao X, Bu W, Lv G, Xu L, Hou D, Wang J, Liu X, Yang T, Zhang X, Liu Q, Gong Y, Shao C. Disrupted mitochondrial homeostasis coupled with mitotic arrest generates antineoplastic oxidative stress. Oncogene. 2022 Jan;41(3):427-443. doi: 10.1038/s41388-021-02105-9. Epub 2021 Nov 12. PMID: 34773075; PMCID: PMC8755538. 5: Chen H, Afrin S, Guo Y, Chu W, Benzinger TLS, Rogers BE, Garbow JR, Perlmutter JS, Zhou D, Xu J. Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-methylpyrimidine-2, 4-diamine (TH287): A Potential Radiotracer for Measuring and Imaging MTH1. Int J Mol Sci. 2020 Nov 23;21(22):8860. doi: 10.3390/ijms21228860. PMID: 33238630; PMCID: PMC7700685. 6: Huang X, Chen J, Wu W, Yang W, Zhong B, Qing X, Shao Z. Delivery of MutT homolog 1 inhibitor by functionalized graphene oxide nanoparticles for enhanced chemo-photodynamic therapy triggers cell death in osteosarcoma. Acta Biomater. 2020 Jun;109:229-243. doi: 10.1016/j.actbio.2020.04.009. Epub 2020 Apr 12. PMID: 32294550. 7: Farand J, Kropf JE, Blomgren P, Xu J, Schmitt AC, Newby ZE, Wang T, Murakami E, Barauskas O, Sudhamsu J, Feng JY, Niedziela-Majka A, Schultz BE, Schwartz K, Viatchenko-Karpinski S, Kornyeyev D, Kashishian A, Fan P, Chen X, Lansdon EB, Ports MO, Currie KS, Watkins WJ, Notte GT. Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation. ACS Med Chem Lett. 2019 Nov 19;11(3):358-364. doi: 10.1021/acsmedchemlett.9b00420. PMID: 32184970; PMCID: PMC7074220. 8: Zhan D, Zhang X, Li J, Ding X, Cui Y, Jia J. MTH1 Inhibitor TH287 Suppresses Gastric Cancer Development Through the Regulation of PI3K/AKT Signaling. Cancer Biother Radiopharm. 2020 Apr;35(3):223-232. doi: 10.1089/cbr.2019.3031. Epub 2020 Feb 20. PMID: 32077746. 9: 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. 10: 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. 11: Hu JJ, Chen Y, Li ZH, Peng SY, Sun Y, Zhang XZ. Augment of Oxidative Damage with Enhanced Photodynamic Process and MTH1 Inhibition for Tumor Therapy. Nano Lett. 2019 Aug 14;19(8):5568-5576. doi: 10.1021/acs.nanolett.9b02112. Epub 2019 Jul 5. PMID: 31262183. 12: Chen C, Li X, Gu M, Di R, Kang N, Wang L, Lai Y, Liu Y, Ji X. Biological characterisation and application of human MTH1 and monoclonal antibody preparation. Oncol Rep. 2019 Mar;41(3):1851-1862. doi: 10.3892/or.2018.6942. Epub 2018 Dec 19. PMID: 30569141. 13: Shi XL, Li Y, Zhao LM, Su LW, Ding G. Delivery of MTH1 inhibitor (TH287) and MDR1 siRNA via hyaluronic acid-based mesoporous silica nanoparticles for oral cancers treatment. Colloids Surf B Biointerfaces. 2019 Jan 1;173:599-606. doi: 10.1016/j.colsurfb.2018.09.076. Epub 2018 Sep 29. PMID: 30352381. 14: Abbas HHK, Alhamoudi KMH, Evans MD, Jones GDD, Foster SS. MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good? BMC Cancer. 2018 Apr 16;18(1):423. doi: 10.1186/s12885-018-4332-7. PMID: 29661172; PMCID: PMC5903006. 15: Li X, Li L, Huang Y, Liu B, Chi H, Shi L, Zhang W, Li G, Niu Y, Zhu X. Synergistic therapy of chemotherapeutic drugs and MTH1 inhibitors using a pH- sensitive polymeric delivery system for oral squamous cell carcinoma. Biomater Sci. 2017 Sep 26;5(10):2068-2078. doi: 10.1039/c7bm00395a. PMID: 28744533. 16: Wang M, Zhou S, Chen Q, Wang L, Liang Z, Wang J. Understanding the molecular mechanism for the differential inhibitory activities of compounds against MTH1. Sci Rep. 2017 Jan 11;7:40557. doi: 10.1038/srep40557. PMID: 28074893; PMCID: PMC5225434. 17: Kawamura T, Kawatani M, Muroi M, Kondoh Y, Futamura Y, Aono H, Tanaka M, Honda K, Osada H. Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival. Sci Rep. 2016 May 23;6:26521. doi: 10.1038/srep26521. PMID: 27210421; PMCID: PMC4876372. 18: Saleh A, Gökturk C, Warpman-Berglund U, Helleday T, Granelli I. Development and validation of method for TH588 and TH287, potent MTH1 inhibitors and new anti-cancer agents, for pharmacokinetic studies in mice plasma. J Pharm Biomed Anal. 2015 Feb;104:1-11. doi: 10.1016/j.jpba.2014.11.009. Epub 2014 Nov 15. PMID: 25459754. 19: Gad H, Koolmeister T, Jemth AS, Eshtad S, Jacques SA, Ström CE, Svensson LM, Schultz N, Lundbäck T, Einarsdottir BO, Saleh A, Göktürk C, Baranczewski P, Svensson R, Berntsson RP, Gustafsson R, Strömberg K, Sanjiv K, Jacques- Cordonnier MC, Desroses M, Gustavsson AL, Olofsson R, Johansson F, Homan EJ, Loseva O, Bräutigam L, Johansson L, Höglund A, Hagenkort A, Pham T, Altun M, Gaugaz FZ, Vikingsson S, Evers B, Henriksson M, Vallin KS, Wallner OA, Hammarström LG, Wiita E, Almlöf I, Kalderén C, Axelsson H, Djureinovic T, Puigvert JC, Häggblad M, Jeppsson F, Martens U, Lundin C, Lundgren B, Granelli I, Jensen AJ, Artursson P, Nilsson JA, Stenmark P, Scobie M, Berglund UW, Helleday T. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature. 2014 Apr 10;508(7495):215-21. doi: 10.1038/nature13181. Epub 2014 Apr 2. Erratum in: Nature. 2017 Apr 26;544(7651):508. doi: 10.1038/nature22083. PMID: 24695224.

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