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Purity: ≥98%
UNC-2025 HCl (known also as UNC2025), the Hydrochloride salt of UNC-2025, is an orally bioavailable and selective MER/FLT3 dual inhibitor with potential antineoplastic activity. With IC50s of 0.74 nM and 0.8 nM, respectively, it inhibits the MER/FLT3 kinases. Inhibiting MER/FLT3 over Axl and Tyro3 was about 20 times more selectively inhibited by UNC 2025. In addition to its strong anti-proliferative activity in vitro and high in vivo antitumor efficacy, UNC-2025 has the ability to inhibit Mer phosphorylation in vivo.
| Targets |
Mer (IC50 = 0.74 nM); FLT3 (IC50 = 0.8 nM); Axl (IC50 = 14 nM); Tyro3 (IC50 = 17 nM)
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|---|---|
| ln Vitro |
UNC2025 has IC50 values of 0.35 nM, 0.46 nM, 1.65 nM, 1.67 nM, 4.38 nM, 5.75 nM, 5.83 nM, 6.14 nM, 7.97 nM, 8.18 nM, and 364 nM against FLT3, MER, AXL, TRKA, TRKC, QIK, TYRO3, SLK, NuaK1, KIT, and Met, respectively[1].
UNC2025 (0-60 nM; 1 hour) effectively inhibits Mer phosphorylation at an IC50 of 2.7 nM in 697 B-ALL cells[1]. UNC2025 (0-60 nM; 1 hour) results in Flt3-ITD positive Molm-14 acute myeloid leukemia cells having reduced Flt3 phosphorylation with an IC50 of 14 nM[1]. UNC2025 (3 nM-3 μM; 1 hour) reduces the expression of p-MEK, p-AXL, and p-TYRO3 in 32D cells in a concentration-dependent manner[1]. UNC2025 (14 nM–10 μM; 48 hours) suppresses MERTK signaling and colony-forming ability in a patient sample that expresses MERTK, with MERTK-expressing leukemia blasts exhibiting a 20-fold increase in sensitivity compared to normal cord or marrow blood mononuclear cells[2]. UNC2025 (25-300 nM; 1 hour) inhibits MERTK, which in turn correlates with a decrease in the phosphorylation of previously identified MERTK-dependent signaling components, including STAT6, AKT, and ERK1/2. Mediates strong and dose-dependent decreases in MERTK phosphorylation/activation in both cell lines[2]. |
| ln Vivo |
UNC2025 (intravenous injection or oral adminstration; 3 mg/kg) demonstrates exceptional pharmacokinetic characteristics, including low clearance (9.2 mL/min kg), extended half-life (3.8 h), and 100% oral exposure. Its Tmax, Cmax, and AUClast values are 0.50 hour, 1.6 μM, and 9.2 h μM, respectively[2].
UNC2025 (orally adminstration; 50 or 75 mg/kg; 34 and 70 days) mediates a dose-dependent tumor burden reduction that is statistically significant when compared to the vehicle. facilitates dose-dependent increases in the median survival in mice receiving vehicle treatment, which is 26 days after treatment initiation, to 34 and 70 days in mice receiving 50 or 75 mg/kg UNC2025, respectively[2]. |
| Enzyme Assay |
UNC2025 hydrochloride is a potent, orally bioavailable dual inhibitor of Mer/Flt3 with an IC50 of 0.8/0.74 nM for Mer/Flt3.
|
| Cell Assay |
UNC-2025 significantly inhibits colony formation in A549 NSCLC and Molm-14 AML cell lines, a function of Mer8 and Flt3. UNC-2025 suppresses downstream MERTK oncogenic signaling, including basal and stimulated pAKT and pERK1/2, in the H2228 and H1299 cell lines. UNC-2025 also reduces colony formation and induces apoptotic cell death in four NSCLC cell lines.
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| Animal Protocol |
NSG mice injected with 697 B-ALL cells[2]
50 or 75 mg/kg Oral adminstration |
| References |
| Molecular Formula |
C28H41CLN6O
|
|---|---|
| Molecular Weight |
513.12
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| Exact Mass |
512.3030376
|
| CAS # |
2070015-17-5
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| Related CAS # |
UNC2025;1429881-91-3
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| Appearance |
Solid
|
| SMILES |
CCCCNC1=NC=C2C(=CN(C2=N1)C3CCC(CC3)O)C4=CC=C(C=C4)CN5CCN(CC5)C.Cl
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| InChi Key |
NYHAEAZNSGIAPV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H40N6O.ClH/c1-3-4-13-29-28-30-18-25-26(20-34(27(25)31-28)23-9-11-24(35)12-10-23)22-7-5-21(6-8-22)19-33-16-14-32(2)15-17-33;/h5-8,18,20,23-24,35H,3-4,9-17,19H2,1-2H3,(H,29,30,31);1H
|
| Chemical Name |
4-[2-(butylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol;hydrochloride
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| Synonyms |
UNC-2025 HCl; UNC-2025 hydrochloride; UNC2025 hydrochloride; UNC 2025 HCl; UNC2025 HCl; UNC 2025 hydrochloride; UNC-2025; UNC2025; UNC 2025
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (194.9 mM)
Ethanol: ~60 mg/mL (116.9 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (1.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 100 mg/mL (194.89 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9489 mL | 9.7443 mL | 19.4886 mL | |
| 5 mM | 0.3898 mL | 1.9489 mL | 3.8977 mL | |
| 10 mM | 0.1949 mL | 0.9744 mL | 1.9489 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01979536 | Active Recruiting |
Drug: Crizotinib Drug: Cytarabine |
Anaplastic Large Cell Lymphoma, ALK-Positive C Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma |
National Cancer Institute (NCI) |
November 8, 2013 | Phase 2 |
| NCT01606878 | Completed | Drug: Crizotinib Drug: Vincristine Sulfate |
Childhood Solid Neoplasm Recurrent Neuroblastoma |
Children's Oncology Group | April 29, 2013 | Phase 1 |
| NCT01998126 | Completed | Drug: Ipilimumab Drug: Crizotinib |
Non-small Cell Lung Cancer | University of Utah | December 2, 2013 | Phase 1 |
| NCT00965731 | Completed | Drug: Erlotinib Drug: PF-02341066 |
Non-Small Cell Lung Cancer | Pfizer | January 2010 | Phase 1 |
| NCT01801111 | Completed | Drug: Erlotinib Drug: Alectinib |
Non-Small-Cell Lung Carcinoma | Hoffmann-La Roche | June 20, 2013 | Phase 1 Phase 2 |
UNC2025 Inhibits Signaling Pathways Downstream of MERTK. Mol Cancer Ther. 2015 Sep; 14(9): 2014–2022. |
UNC2025 Inhibits NSCLC tumor growth in vivo: H2228 (A) or A549 (B,C). Mol Cancer Ther. 2015 Sep; 14(9): 2014–2022. |
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