TP-3654 | CAS#1361951-15-6 | Pim-1 & Pim-3 Kinase Inhibitor

MedKoo Cat#: 527505 | Name: TP-3654

Description:

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

TP-3654 is a Pim-1 and Pim-3 kinase inhibitor potentially for the treatment of prostate cancer, acute myeloid leukemia, multiple sclerosis and psoriasis. TP-3654 displays favorable human ether-à-go-go-related gene and cytochrome P450 inhibition profiles compared with the first-generation PIM inhibitor, SGI-1776, and exhibits oral bioavailability.

Chemical Structure

TP-3654

CAS#1361951-15-6 (free base)

Theoretical Analysis

MedKoo Cat#: 527505

Name: TP-3654

CAS#: 1361951-15-6 (free base)

Chemical Formula: C22H25F3N4O

Exact Mass: 418.1980

Molecular Weight: 418.46

Elemental Analysis: C, 63.15; H, 6.02; F, 13.62; N, 13.39; O, 3.82

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 1,350.00	Ready to ship

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Related CAS #

1418143-09-5 (HCl) 1361951-15-6 (free base)

Synonym

TP-3654; TP3654; TP 3654;

IUPAC/Chemical Name

2-((1r,4r)-4-((3-(3-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-6-yl)amino)cyclohexyl)propan-2-ol

InChi Key

XRNVABDYQLHODA-JCNLHEQBSA-N

InChi Code

InChI=1S/C22H25F3N4O/c1-21(2,30)15-6-8-17(9-7-15)27-19-10-11-20-26-13-18(29(20)28-19)14-4-3-5-16(12-14)22(23,24)25/h3-5,10-13,15,17,30H,6-9H2,1-2H3,(H,27,28)/t15-,17-

SMILES Code

OC(C)(C)[C@H]1CC[C@H](NC2=NN3C(C=C2)=NC=C3C4=CC=CC(C(F)(F)F)=C4)CC1

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

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#B7B08C04

QC Data

View QC data: current batch, Lot#B7B08C04

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

TP-3654 is a second-generation Pim kinase inhibitor with Ki values of 5 and 42 nM for Pim-1 and Pim-3, respectively.

In vitro activity:

The cellular potency of TP-3654 was determined by measuring its effect on baseline phosphorylation of BAD, a known substrate of PIM, on serine 112 by overexpression of PIM-1 and BAD in HEK-293 cells. Overexpression of the catalytically inactive mutant PIM-1 (K67M) did not increase phosphorylation of BAD compared to BAD transfection alone (Figure 2A) and was used as a negative control to subtract BAD phosphorylation by cellular kinases other than PIM-1. TP-3654 demonstrated potent PIM-1 specific cellular activity in the PIM-1/BAD overexpression system with an average EC50 = 67 nM (Figure 1C). In addition, TP-3654 treatment reduced levels of phospho-BAD in vitro using the bladder cancer cell line UM-UC-3 (Figure 2B). To exclude the possibility that this phospho-BAD decrease was due to off-target activity, we measured levels of phospho-4EBP1 in parallel with phospho-BAD. There was no appreciable difference in levels of phospho-4EBP1 in TP-3654–treated cells (Figure 2B), providing further evidence that PIM inhibition was the primary mechanism for the phospho-BAD decrease observed in TP-3654–treated cells and not activity of the compound inhibiting AKT, another known kinase that can phosphorylate BAD. Reference: Neoplasia. 2014 May;16(5):403-12. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24953177/

In vivo activity:

It was tested whether TP-3654 could inhibit the growth of established mouse xenograft tumors using the UM-UC-3 and PC-3 solid tumor cell lines. Oral dosing of 200 mg/kg TP-3654 significantly reduced both UM-UC-3 and PC-3 tumor growth measured by volume (caliper) and by final tumor weight, with no significant changes in body weight or gross adverse toxicity (Figure 5). Reference: Neoplasia. 2014 May;16(5):403-12. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24953177/

	Solvent	mg/mL	mM
Solubility
	DMSO	86.0	200.74
	Ethanol	6.0	14.34

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 418.46 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:

In vitro protocol:

1. Foulks JM, Carpenter KJ, Luo B, Xu Y, Senina A, Nix R, Chan A, Clifford A, Wilkes M, Vollmer D, Brenning B, Merx S, Lai S, McCullar MV, Ho KK, Albertson DJ, Call LT, Bearss JJ, Tripp S, Liu T, Stephens BJ, Mollard A, Warner SL, Bearss DJ, Kanner SB. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014 May;16(5):403-12. doi: 10.1016/j.neo.2014.05.004. Epub 2014 Jun 18. PMID: 24953177; PMCID: PMC4198696. 2. Whillock AL, Mambetsariev N, Lin WW, Stunz LL, Bishop GA. TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells. Sci Rep. 2019 Sep 9;9(1):12884. doi: 10.1038/s41598-019-49390-9. Erratum in: Sci Rep. 2019 Nov 20;9(1):17502. PMID: 31501481; PMCID: PMC6733949.

In vivo protocol:

1. Foulks JM, Carpenter KJ, Luo B, Xu Y, Senina A, Nix R, Chan A, Clifford A, Wilkes M, Vollmer D, Brenning B, Merx S, Lai S, McCullar MV, Ho KK, Albertson DJ, Call LT, Bearss JJ, Tripp S, Liu T, Stephens BJ, Mollard A, Warner SL, Bearss DJ, Kanner SB. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014 May;16(5):403-12. doi: 10.1016/j.neo.2014.05.004. Epub 2014 Jun 18. PMID: 24953177; PMCID: PMC4198696. 2. Lampron MC, Vitry G, Nadeau V, Grobs Y, Paradis R, Samson N, Tremblay È, Boucherat O, Meloche J, Bonnet S, Provencher S, Potus F, Paulin R. PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension. Arterioscler Thromb Vasc Biol. 2020 Mar;40(3):783-801. doi: 10.1161/ATVBAHA.119.313763. Epub 2020 Jan 23. PMID: 31969012.

1: Foulks JM, Carpenter KJ, Luo B, Xu Y, Senina A, Nix R, Chan A, Clifford A, Wilkes M, Vollmer D, Brenning B, Merx S, Lai S, McCullar MV, Ho KK, Albertson DJ, Call LT, Bearss JJ, Tripp S, Liu T, Stephens BJ, Mollard A, Warner SL, Bearss DJ, Kanner SB. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014 May;16(5):403-12. doi: 10.1016/j.neo.2014.05.004. PubMed PMID: 24953177; PubMed Central PMCID: PMC4198696. 2: Thakur ML, Marcus CS, Saeed S, Pallela V, Minami C, Diggles L, Le Pham H, Ahdoot R, Kalinowski EA. 99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans. J Nucl Med. 2000 Jan;41(1):107-10. PubMed PMID: 10647612. 3: Thakur ML, Marcus CS, Saeed S, Pallela V, Minami C, Diggles L, Pham HL, Ahdoot R, Kalinowski EA, Moody T. Imaging tumors in humans with Tc-99m-VIP. Ann N Y Acad Sci. 2000;921:37-44. PubMed PMID: 11193855. 4: Thakur ML, Aruva MR, Gariepy J, Acton P, Rattan S, Prasad S, Wickstrom E, Alavi A. PET imaging of oncogene overexpression using 64Cu-vasoactive intestinal peptide (VIP) analog: comparison with 99mTc-VIP analog. J Nucl Med. 2004 Aug;45(8):1381-9. PubMed PMID: 15299065. 5: Rao PS, Thakur ML, Pallela V, Patti R, Reddy K, Li H, Sharma S, Pham HL, Diggles L, Minami C, Marcus CS. 99mTc labeled VIP analog: evaluation for imaging colorectal cancer. Nucl Med Biol. 2001 May;28(4):445-50. PubMed PMID: 11395318. 6: Pallela VR, Thakur ML, Chakder S, Rattan S. 99mTc-labeled vasoactive intestinal peptide receptor agonist: functional studies. J Nucl Med. 1999 Feb;40(2):352-60. PubMed PMID: 10025846.