This product has been discontinued from InvivoChem due to commercial reason.
Purity: ≥98%
This product has been discontinued from InvivoChem. UM729 (also known as UM-729; UM 729; C-07; C 07; C07) is an enhancer of aryl hydrocarbon receptor (AhR) antagonists. UM-729 enhances the self-renewal of human hematopoietic stem cells in vitro. UM729 has been found to be a new pyrimidoindole and have an additive efficacy with AhR antagonists in preventing differentiation in most AML specimen. In addition, UM729 has been reported to expand mormal HSPCs in a AhR-independent fashion.
| Targets |
As a pyrimido-indole derivative, this compound does not inhibit aryl hydrocarbon receptor (AhR) target genes and promotes the expansion of normal hematopoietic stem and progenitor cells (HSPCs) in an AhR-independent manner. Studies have shown that UM729 acts by modulating the Hippo signaling pathway, significantly increasing the protein levels of YAP (a key Hippo pathway regulator) predominantly in the cytoplasm, suggesting potential inhibitory effects on this pathway.
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| ln Vitro |
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| ln Vivo |
In NSG mice, UM729 increases engraftment but not leukemic stem cell (LSC) frequency when administered alone or in combination with SR1.
In vivo studies demonstrate that in NSG mice, UM729 administered alone or in combination with SR1 increases AML cell engraftment but does not increase leukemic stem cell (LSC) frequency. In HSPC differentiation studies, UM729-derived HSPCs show good functionality, providing a new cell source option for cell therapy of blood diseases. |
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| Cell Assay |
HSPC Differentiation Assay: Using a directed differentiation protocol for hiPSCs, UM729 (0.1, 1, 10 μM) is added on day 7 of differentiation. On day 12, CD34+CD45+CD90+ HSPC marker expression is detected by flow cytometry.
AML Cell Differentiation Inhibition Assay: Human AML cells (05H163 cells) are treated with UM729 (1 μM) in combination with AhR inhibitors for 4 days, and the percentage of CD34+CD15- cells is detected by flow cytometry.
HSPC Expansion Assay: CD34+ cells are cultured in SFEMII medium supplemented with SCF, Flt-3L, IL-3, IL-6, and BIT 9500, with UM729 (1 μM) added. Cells are passaged every two days and collected on day 10 for flow cytometry analysis.
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| Animal Protocol |
Animal Model: NSG immunodeficient mice are used as the transplantation model.
Cell Preparation: Human AML cells are labeled with CellTrace Violet and pre-incubated with SR1 (500 nM) and/or UM729 (1 μM) prior to transplantation.
Dosing Regimen: Treated AML cells are transplanted into NSG mice via intravenous (i.v.) injection.
Efficacy Assessment: AML cell engraftment rates and leukemic stem cell (LSC) frequency in mice are monitored to evaluate the effect of UM729 on transplantation outcomes.
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| ADME/Pharmacokinetics |
The compound has good solubility in DMSO (approximately 48 mg/mL, 130.6 mM) but low solubility in water (<1 mg/mL); solubility information in ethanol is limited. In animal studies, UM729 is administered via intravenous (i.v.) injection at a concentration of 1 μM.
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| References |
Nat Methods.2014Apr;11(4):436-42.
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| Molecular Formula |
C20H25N5O2
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| Molecular Weight |
367.4448
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| Exact Mass |
367.2
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| CAS # |
1448723-60-1
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| Related CAS # |
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| PubChem CID |
71714933
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
611.1±55.0 °C at 760 mmHg
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| Flash Point |
323.4±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.677
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
499
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=CC2=C(C=C1)C3=C(NCCCN4CCCCC4)N=CN=C3N2)OC
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| InChi Key |
SIBCJMZHJZDUNK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H25N5O2/c1-27-20(26)14-6-7-15-16(12-14)24-19-17(15)18(22-13-23-19)21-8-5-11-25-9-3-2-4-10-25/h6-7,12-13H,2-5,8-11H2,1H3,(H2,21,22,23,24)
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| Chemical Name |
methyl 4-(3-piperidin-1-ylpropylamino)-9H-pyrimido[4,5-b]indole-7-carboxylate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7215 mL | 13.6077 mL | 27.2153 mL | |
| 5 mM | 0.5443 mL | 2.7215 mL | 5.4431 mL | |
| 10 mM | 0.2722 mL | 1.3608 mL | 2.7215 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.
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