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UM 171HSC agonist

UM 171

Catalog No. A8950
Size Price Stock Qty
5mg $132.00 In stock
25mg $430.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Protocol

Cell experiment: [1]

Cell lines

CD34+ CB cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reacting condition

35 nM, for different time point treatment.

Applications

Cells were treated with 35 nM UM171 for 3, 12, 24, 48 and 72 hours. At each time point, cells were lysed, RNA was extracted and sequenced. UM171 treatment was accompanied by a marked suppression of transcripts associated with erythroid and megakaryocytic differentiation. Only six to seven genes were commonly up- or down- regulated in cells exposed to UM171. The most highly up-regulated genes in UM171-treated cells encode for surface molecules. These genes include PROCR (also called EPCR or CD201), which represents a known marker of mouse LT-HSCs.

Animal experiment: [1]

Animal models

Female NSG mice

Dosage form

35 nM treated with CD34+ CB cells

Application

NSG mice were injected with CD34+ CB cells that had been originally cultured in DMSO or UM171. Levels of human cell engraftment were determined for ~300 mice and represented in the form of a heat map. Analysis of this dataset indicates two emerging patterns of human reconstitution, one from predominantly lymphomyeloid LT-HSCs, observed at high cell doses with most conditions, and the other from LT-HSCs that display a lymphoid-deficient differentiation phenotype mostly observed with UM171 treatment. Neither B lymphopoiesis nor the frequency or number of lymphomyeloid LT-HSCs is negatively affected by UM171. The impact of UM171 on LT-HSC was preserved at 30 weeks posttransplantation, at which time multilineage contribution remained obvious at the high cell dose.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Fares I, Chagraoui J, Gareau Y, et al. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal. Science, 2014, 345(6203): 1509-1512.

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Chemical Properties

Cas No. 1448724-09-1 SDF Download SDF
Chemical Name (1r,4r)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine
Canonical SMILES N[C@@H](CC1)CC[C@H]1NC2=NC(CC3=CC=CC=C3)=NC(N4)=C2C5=C4C=C(C6=NN(C)N=N6)C=C5
Formula C25H27N9 M.Wt 453.54
Solubility Soluble in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Background

UM171 is a selective agonist of human hematopoietic stem cell self-renewal [1].

UM171 is a synthesized analog of UM729, which is screened out for its ability to expand human CD34+ CD45RA– mobilized peripheral blood cells. UM171 was 10- to 20- fold more potent than UM729 with efficacious concentrations of 17 to 19 nM. UM171 treatment enhanced the engraftment potential of CD34+ macaque cells by threefold. It was also found that UM171 had no direct effect on mitosis and no effect on the division rate of phenotypically primitive populations. In addition, UM171 showed cooperation with StemRegenin (SR1) to enhance expansion of short-lived progenitors while UM171 itself selectively enhanced the long-term-HSCs. Moreover, in NSG mice, UM171 exerted effects on lymphoid-deficient differentiation in human hematopoietic reconstitution obtained by transplanting fresh or expanded cells [1].

References:
[1] Fares I, Chagraoui J, Gareau Y, et al. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal. Science, 2014, 345(6203): 1509-1512.