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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
NCGC00379308, formerly known as D3-ßArr, is a Positive Allosteric Modulator (PAM) of the TSH receptor. D3-ßArr potentiates the effect of TSH in stimulating β-Arr 1 translocation.
Molecular Formula |
C20H23N5
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Molecular Weight |
333.43012
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Exact Mass |
333.195
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CAS # |
662164-09-2
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Related CAS # |
662164-09-2;
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PubChem CID |
2950121
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Appearance |
White to off-white solid powder
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LogP |
3.6
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Hydrogen Bond Donor Count |
2
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Hydrogen Bond Acceptor Count |
5
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Rotatable Bond Count |
4
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Heavy Atom Count |
25
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Complexity |
405
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Defined Atom Stereocenter Count |
0
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SMILES |
C1(C(NC2C3C(=CC=CC=3)N=C(N3CCNCC3)N=2)C)C=CC=CC=1
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InChi Key |
LOGWGZNWEWFTJV-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C20H23N5/c1-15(16-7-3-2-4-8-16)22-19-17-9-5-6-10-18(17)23-20(24-19)25-13-11-21-12-14-25/h2-10,15,21H,11-14H2,1H3,(H,22,23,24)
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Chemical Name |
N-(1-Phenylethyl)-2-(1-piperazinyl)-4-quinazolinamine
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Synonyms |
D3-ßArr D3ßArr D3 ßArr NCGC00379308 NCGC-00379308 NCGC 00379308
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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 : ≥ 125 mg/mL (~374.89 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.24 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.08 mg/mL (6.24 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 20.8 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: ≥ 2.08 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.9991 mL | 14.9957 mL | 29.9913 mL | |
5 mM | 0.5998 mL | 2.9991 mL | 5.9983 mL | |
10 mM | 0.2999 mL | 1.4996 mL | 2.9991 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.
D3-βArr is a functionally selective TSHR agonist of β-Arr 1-mediated signaling and does not antagonize TSH-induced cAMP production. (A) DiscoverX1 cells were exposed to 0.18 μM TSH or 10 μM D3-βArr in HBSS with 1 mM IBMX for 1 hour. cAMP levels were measured by ELISA. In contrast to TSH, D3-βArr-induced activation of the TSHR does not lead to cAMP production. The data are from three experiments with duplicate samples. (B and C) TSH does not antagonize TSHR stimulation of cAMP production. (B) DiscoverX1 cells were pretreated with DMSO (Basal) or 10 μM D3-βArr in HBSS for 30 minutes. Subsequently, cells were exposed to 18 nM TSH (EC50) with or without 10 μM D3-βArr in HBSS with 1 mM IBMX for 1 hour. cAMP levels were measured by ELISA. The data are from three experiments with duplicate samples. (C) Primary cultures of human thyrocytes from five different donors were studied. Cells were pretreated with DMSO (basal) or 10 µM D3-βArr in HBSS/HEPES for 1 hour. Subsequently, cells were exposed to 90 nM TSH (EC50 for cAMP in human thyrocytes) with or without 10 μM D3-βArr in HBSS with 1 mM IBMX for 2 hours at 37°C. Incubations were stopped, the cells were lysed, and cAMP levels were measured by ELISA. (A–C) The data are presented as means ± S.D. Statistical significance is determined by unpaired two-tailed t test (****P < 0.0001; N.S., not significant). J Pharmacol Exp Ther. 2018 Jan;364(1):38-45. td> |
D3-βArr is a positive allosteric modulator for TSH-induced upregulation of OPN and ALPL mRNAs in U2OS-TSHR cells. Cells were treated with the indicated doses of TSH with and without 10 μM D3-βArr in EMEM with 0.1% BSA. The data represent the gene expression levels of osteoblastic markers OPN and ALPL after 7 days of incubation with ligands. Samples were analyzed by quantitative RT-PCR. The data are from three experiments with duplicate samples and are presented as means ± S.D. Statistical significance is determined by unpaired two-tailed t test (**P < 0.01; ***P < 0.001; ****P < 0.0001). J Pharmacol Exp Ther. 2018 Jan;364(1):38-45. td> |
The potentiating effect of D3-βArr on TSH-induced OPN secretion is mediated by β-Arr 1 in U2OS-TSHR cells. Cells were transfected with nontargeting (CONTROL), β-Arr 1 (ARR1), and β-Arr 2 (ARR2) siRNAs, respectively. (A) Knockdown of ARR1 and ARR2 is demonstrated by RT-PCR. ARR1 and ARR2 mRNAs were measured 72 hours after transfection. The mRNA level in nontreated control cells was set at 100%. The data are from four independent experiments with duplicate samples and are presented as mean ± S.D. (B) 72 hours after transfection with siRNA, the cells were treated with 1.8 µM TSH with and without 10 µM D3-βArr in EMEM with 0.1% BSA for 5 days. OPN secretion was determined by measurement of OPN by ELISA in cell culture medium. The bars represent the means ± S.D. of four experiments with duplicate samples. Statistical significance is determined by unpaired two-tailed t test (*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; N.S., not significant). J Pharmacol Exp Ther. 2018 Jan;364(1):38-45. td> |