PTC-209 | CAS#315704-66-6 | BMI-1 inhibitor

MedKoo Cat#: 406517 | Name: PTC-209

Description:

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

PTC-209 is a potent BMI-1 inhibitor with potential anticancer activity. PTC-209 inhibits endogenous BMI-1 expression in human colorectal HCT116 and human fibrosarcoma HT1080 tumor cells. PTC-209 decreases colorectal tumor cell growth in a BMI-1-dependent way. In addition, PTC-209 impairs colorectal cancer-initiating cells (CICs) through irreversible growth inhibition.

Chemical Structure

PTC-209

CAS#315704-66-6 (free base)

Theoretical Analysis

MedKoo Cat#: 406517

Name: PTC-209

CAS#: 315704-66-6 (free base)

Chemical Formula: C17H13Br2N5OS

Exact Mass: 492.9208

Molecular Weight: 495.19

Elemental Analysis: C, 41.23; H, 2.65; Br, 32.27; N, 14.14; O, 3.23; S, 6.48

Price and Availability

Size	Price	Availability
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
200mg	USD 1,250.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 2,950.00	2 Weeks
2g	USD 5,250.00	2 Weeks

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Related CAS #

1217022-63-3 (HBr) 315704-66-6 (free base)

Synonym

PTC209; PTC 209; PTC-209.

IUPAC/Chemical Name

N-(2,6-dibromo-4-methoxyphenyl)-4-(2-methylimidazo[1,2-a]pyrimidin-3-yl)thiazol-2-amine

InChi Key

XVOOCQSWCCRVDY-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H13Br2N5OS/c1-9-15(24-5-3-4-20-16(24)21-9)13-8-26-17(22-13)23-14-11(18)6-10(25-2)7-12(14)19/h3-8H,1-2H3,(H,22,23)

SMILES Code

CC1=C(C2=CSC(NC3=C(Br)C=C(OC)C=C3Br)=N2)N4C=CC=NC4=N1

Appearance

Beige to grey 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A20T10K24

View CoA: current batch, Lot#CRB41229

QC Data

View QC data: current batch, Lot#A20T10K24

View QC data: current batch, Lot#CRB41129

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PTC-209 is a specific BMI-1 inhibitor with an IC50 of 0.5 μM in HEK293T cell line.

In vitro activity:

The numbers of both LNM35 and A549 cells after 48 h treatment with PTC-209 were lower than the numbers of cells at 0 h hence, suggesting the occurrence of cell death upon PTC-209 treatment. Tesults clearly show that PTC-209 (2.5 μM) not only significantly reduced the cellular proliferation of lung cancer cells but also induced cellular death (Figures 4A, B). The level of active caspase 3/7, a marker of apoptosis, in PTC-209-treated cells was determined. Although a concentration of 1 and 2.5 μM, which dramatically reduced cell viability, had no effect on caspase 3/7 activation in all cancer cell lines tested, a mild but significant 1.46-fold increase in caspase 3/7 was seen in A549 cells treated with 2.5 μM of PTC-209 (Figure 4C). Taken together, results strongly suggest that PTC-209 exerts its anticancer activity through the inhibition of cellular proliferation and the induction of cellular death presumably independent of caspase 3/7 mechanism. Reference: Front Pharmacol. 2019; 10: 1199. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815748/

In vivo activity:

Reduced expression of Bmi1 by PTC-209 was accompanied by an increase in the fraction of p16+ and SA-β-gal+ cells (Figure 5, B and C). There was also a profound reduction in Sox2 expression in p-Akt+ tumor lesions of PTC-209-treated mice (38.8 [2.3]% from 10 grafts in vehicle vs 6.1 [1.4]% from 10 grafts in PTC-209, P < .001) as well as human and mouse prostate cancer cell lines (Figure 5, D–F). To test the effects of targeting Bmi1 and Sox2 on tumor recurrence, a trial of PTC-209 in SCID mice harboring BC-Pten grafts in which mice were treated with PTC-209 for 21 days beginning a month after castration (Figure 6A) was conducted. Mice were followed-up to the endpoint of 5 months after castration for this experiment. Downregulation of Bmi1 and Sox2 as well as upregulation of p16 in PTC-209-treated grafts was confirmed as pharmacodynamic measures of the drug (Supplementary Figure 5C, available online). Pathological analysis of H&E (hematoxylin and eosin)-stained sections showed a statistically significant reduction in PIN (prostatic intraepithelial neoplasia)/cancer incidence in PTC-209-treated grafts (100% in vehicle-treated grafts vs 58.3% in PTC-209-treated grafts, P < .001) concomitant with a reduction in proliferation (10.6 [1.1]% in vehicle-treated grafts vs 3.1 [0.2]% in PTC-209-treated grafts, P=.001) (Figure 6, B–D), indicating that targeting Bmi1+Sox2+ cells with PTC-209 impairs prostate cancer recurrence after castration in this model. Reference: J Natl Cancer Inst. 2019 Mar; 111(3): 311–321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410937/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.6	96.19
	DMF	5.0	10.10
	DMF:PBS (pH 7.2) (1:7)	0.1	0.20
	Ethanol	9.9	20.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 495.19 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

Formulation protocol:

1. Sulaiman S, Arafat K, Iratni R, Attoub S. PTC-209 Anti-Cancer Effects Involved the Inhibition of STAT3 Phosphorylation. Front Pharmacol. 2019 Oct 21;10:1199. doi: 10.3389/fphar.2019.01199. PMID: 31695609; PMCID: PMC6815748. 2. Dimri M, Kang M, Dimri GP. A miR-200c/141-BMI1 autoregulatory loop regulates oncogenic activity of BMI1 in cancer cells. Oncotarget. 2016 Jun 14;7(24):36220-36234. doi: 10.18632/oncotarget.8811. PMID: 27105531; PMCID: PMC5094995. 3. Shen HT, Chien PJ, Chen SH, Sheu GT, Jan MS, Wang BY, Chang WW. BMI1-Mediated Pemetrexed Resistance in Non-Small Cell Lung Cancer Cells Is Associated with Increased SP1 Activation and Cancer Stemness. Cancers (Basel). 2020 Jul 27;12(8):2069. doi: 10.3390/cancers12082069. PMID: 32726929; PMCID: PMC7463866. 4. Yoo YA, Vatapalli R, Lysy B, Mok H, Desouki MM, Abdulkadir SA. The Role of Castration-Resistant Bmi1+Sox2+ Cells in Driving Recurrence in Prostate Cancer. J Natl Cancer Inst. 2019 Mar 1;111(3):311-321. doi: 10.1093/jnci/djy142. PMID: 30312426; PMCID: PMC6410937.

In vitro protocol:

In vivo protocol:

1. Shen HT, Chien PJ, Chen SH, Sheu GT, Jan MS, Wang BY, Chang WW. BMI1-Mediated Pemetrexed Resistance in Non-Small Cell Lung Cancer Cells Is Associated with Increased SP1 Activation and Cancer Stemness. Cancers (Basel). 2020 Jul 27;12(8):2069. doi: 10.3390/cancers12082069. PMID: 32726929; PMCID: PMC7463866. 2. Yoo YA, Vatapalli R, Lysy B, Mok H, Desouki MM, Abdulkadir SA. The Role of Castration-Resistant Bmi1+Sox2+ Cells in Driving Recurrence in Prostate Cancer. J Natl Cancer Inst. 2019 Mar 1;111(3):311-321. doi: 10.1093/jnci/djy142. PMID: 30312426; PMCID: PMC6410937.

1: Soleiman M, Fathi-Roudsari M, Khajeh K, Maghsoudi A. Optimization of Epigenetic Modifier Drug Combination for Synergistic Effect against Glioblastoma Multiform Cancer Cell Lines. Cancer Invest. 2024 Apr;42(4):319-332. doi: 10.1080/07357907.2024.2345183. Epub 2024 May 2. PMID: 38695671. 2: Zhu M, Fan H, Deng J, Jiang K, Liao J, Zhang X, Chen Y, Yu M, Peng Z. BMI1 Silencing Liposomes Suppress Postradiotherapy Cancer Stemness against Radioresistant Hepatocellular Carcinoma. ACS Nano. 2023 Dec 12;17(23):23405-23421. doi: 10.1021/acsnano.3c04636. Epub 2023 Nov 21. PMID: 37988576. 3: Hua T, Xue Y, Sarker DB, Kiran S, Li Y, Sang QA. Modeling human brain rhabdoid tumor by inactivating tumor suppressor genes in induced pluripotent stem cells. Bioact Mater. 2023 Aug 12;31:136-150. doi: 10.1016/j.bioactmat.2023.08.009. PMID: 37637078; PMCID: PMC10448240. 4: Li W, Solenne TOSB, Wang H, Li B, Liu Y, Wang F, Yang T. Core-shell cisplatin/SiO2 nanocapsules combined with PTC-209 overcome chemotherapy-Acquired and intrinsic resistance in hepatocellular carcinoma. Acta Biomater. 2023 Oct 15;170:273-287. doi: 10.1016/j.actbio.2023.08.021. Epub 2023 Aug 18. PMID: 37597681. 5: Peng M, Wu J, Wang W, Liao T, Xu S, Xiao D, He Z, Yang X. Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1. Front Nutr. 2023 Apr 17;10:1141964. doi: 10.3389/fnut.2023.1141964. PMID: 37139440; PMCID: PMC10150882. 6: Zaczek A, Szustka A, Krześlak A. Glucose and Cell Context-Dependent Impact of BMI-1 Inhibitor PTC-209 on AKT Pathway in Endometrial Cancer Cells. Cancers (Basel). 2022 Dec 1;14(23):5947. doi: 10.3390/cancers14235947. PMID: 36497428; PMCID: PMC9739103. 7: Liu JY, Jiang YN, Huang H, Xu JF, Wu YH, Wang Q, Zhu Y, Zheng B, Shen C, Qian WF, Shen J. BMI-1 promotes breast cancer proliferation and metastasis through different mechanisms in different subtypes. Cancer Sci. 2023 Feb;114(2):449-462. doi: 10.1111/cas.15623. Epub 2022 Nov 10. PMID: 36285479; PMCID: PMC9899611. 8: Zhang C, Yang Y, Wang K, Chen M, Lu M, Hu C, Du X, Xing B, Liu X. The Systematic Analyses of RING Finger Gene Signature for Predicting the Prognosis of Patients with Hepatocellular Carcinoma. J Oncol. 2022 Sep 26;2022:2466006. doi: 10.1155/2022/2466006. PMID: 36199791; PMCID: PMC9529411. 9: Al-Nadaf S, Peacott-Ricardos KS, Dickinson PJ, Rebhun RB, York D. Expression and therapeutic targeting of BMI1 in canine gliomas. Vet Comp Oncol. 2022 Dec;20(4):871-880. doi: 10.1111/vco.12852. Epub 2022 Jul 27. PMID: 35833892. 10: Zhou W, Yun Z, Wang T, Li C, Zhang J. BTF3-mediated regulation of BMI1 promotes colorectal cancer through influencing epithelial-mesenchymal transition and stem cell-like traits. Int J Biol Macromol. 2021 Sep 30;187:800-810. doi: 10.1016/j.ijbiomac.2021.07.106. Epub 2021 Jul 20. PMID: 34293363. 11: Zhang Z, Oh M, Sasaki JI, Nör JE. Inverse and reciprocal regulation of p53/p21 and Bmi-1 modulates vasculogenic differentiation of dental pulp stem cells. Cell Death Dis. 2021 Jun 24;12(7):644. doi: 10.1038/s41419-021-03925-z. PMID: 34168122; PMCID: PMC8225874. 12: Shan W, Zhou L, Liu L, Lin D, Yu Q. Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells. Exp Ther Med. 2021 Jun;21(6):619. doi: 10.3892/etm.2021.10051. Epub 2021 Apr 14. PMID: 33936276; PMCID: PMC8082597. 13: Shields CE, Potlapalli S, Cuya-Smith SM, Chappell SK, Chen D, Martinez D, Pogoriler J, Rathi KS, Patel SA, Oristian KM, Linardic CM, Maris JM, Haynes KA, Schnepp RW. Epigenetic regulator BMI1 promotes alveolar rhabdomyosarcoma proliferation and constitutes a novel therapeutic target. Mol Oncol. 2021 Aug;15(8):2156-2171. doi: 10.1002/1878-0261.12914. Epub 2021 Mar 27. PMID: 33523558; PMCID: PMC8333775. 14: Wang X, Li K, Cheng M, Wang G, Han H, Chen F, Liao W, Chen Z, Chen J, Bao Y, Peng L, Chen D. Bmi1 Severs as a Potential Tumor-Initiating Cell Marker and Therapeutic Target in Esophageal Squamous Cell Carcinoma. Stem Cells Int. 2020 Aug 20;2020:8877577. doi: 10.1155/2020/8877577. PMID: 32884573; PMCID: PMC7455816. 15: Shen HT, Chien PJ, Chen SH, Sheu GT, Jan MS, Wang BY, Chang WW. BMI1-Mediated Pemetrexed Resistance in Non-Small Cell Lung Cancer Cells Is Associated with Increased SP1 Activation and Cancer Stemness. Cancers (Basel). 2020 Jul 27;12(8):2069. doi: 10.3390/cancers12082069. PMID: 32726929; PMCID: PMC7463866. 16: Gao T, Lin M, Shao B, Zhou Q, Wang Y, Chen X, Zhao D, Dai X, Shen C, Cheng H, Yang S, Li H, Zheng B, Zhong X, Yu J, Chen L, Huang X. BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells. Cell Cycle. 2020 Aug;19(15):1884-1898. doi: 10.1080/15384101.2020.1779471. Epub 2020 Jun 28. PMID: 32594840; PMCID: PMC7469621. 17: Testa G, Russo M, Di Benedetto G, Barbato M, Parisi S, Pirozzi F, Tocchetti CG, Abete P, Bonaduce D, Russo T, Passaro F. Bmi1 inhibitor PTC-209 promotes Chemically-induced Direct Cardiac Reprogramming of cardiac fibroblasts into cardiomyocytes. Sci Rep. 2020 Apr 28;10(1):7129. doi: 10.1038/s41598-020-63992-8. PMID: 32346096; PMCID: PMC7189257. 18: Sulaiman S, Arafat K, Iratni R, Attoub S. PTC-209 Anti-Cancer Effects Involved the Inhibition of STAT3 Phosphorylation. Front Pharmacol. 2019 Oct 21;10:1199. doi: 10.3389/fphar.2019.01199. PMID: 31695609; PMCID: PMC6815748. 19: Wang J, Xing Y, Wang Y, He Y, Wang L, Peng S, Yang L, Xie J, Li X, Qiu W, Yi Z, Liu M. A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer. J Exp Clin Cancer Res. 2019 Oct 22;38(1):422. doi: 10.1186/s13046-019-1392-8. PMID: 31640758; PMCID: PMC6805542. 20: Elango R, Vishnubalaji R, Manikandan M, Binhamdan SI, Siyal AA, Alshawakir YA, Alfayez M, Aldahmash A, Alajez NM. Concurrent targeting of BMI1 and CDK4/6 abrogates tumor growth in vitro and in vivo. Sci Rep. 2019 Sep 23;9(1):13696. doi: 10.1038/s41598-019-50140-0. PMID: 31548560; PMCID: PMC6757061.