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MedKoo Cat#: 406758 | Name: DBeQ
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Description:

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

DBeQ, also known as JRF 12, is a selective, reversible, and ATP-competitive inhibitor of the ATPase p97 for treatment of cancer. DBeQ impairs both ubiquitin-dependent and autophagic protein clearance pathways. DBeQ was shown to inhibit the ATPase activity of Vps4 with an IC50 of about 11.5 μM. To a less degree, it also inhibits hyphal growth. DBeQ blocks multiple processes that have been shown by RNAi to depend on p97, including degradation of ubiquitin fusion degradation and endoplasmic reticulum-associated degradation pathway reporters, as well as autophagosome maturation. DBeQ also potently inhibits cancer cell growth and is more rapid than a proteasome inhibitor at mobilizing the executioner caspases-3 and -7.

Chemical Structure

DBeQ
DBeQ
CAS#177355-84-9

Theoretical Analysis

MedKoo Cat#: 406758

Name: DBeQ

CAS#: 177355-84-9

Chemical Formula: C22H20N4

Exact Mass: 340.1688

Molecular Weight: 340.43

Elemental Analysis: C, 77.62; H, 5.92; N, 16.46

Price and Availability

Size Price Availability Quantity
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 400.00 Ready to ship
200mg USD 700.00 Ready to ship
500mg USD 1,350.00 Ready to ship
1g USD 2,350.00 Ready to ship
2g USD 3,850.00 Ready to ship
5g USD 5,950.00 2 weeks
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Synonym
DBeQ; DBEQ; JRF12; JRF-12; JRF 12.
IUPAC/Chemical Name
N2,N4-dibenzylquinazoline-2,4-diamine
InChi Key
QAIMUUJJAJBPCL-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H20N4/c1-3-9-17(10-4-1)15-23-21-19-13-7-8-14-20(19)25-22(26-21)24-16-18-11-5-2-6-12-18/h1-14H,15-16H2,(H2,23,24,25,26)
SMILES Code
C12=CC=CC=C1N=C(NCC3=CC=CC=C3)N=C2NCC4=CC=CC=C4
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, not in water
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
A specific small-molecule inhibitor of p97 would provide an important tool to investigate diverse functions of this essential ATPase associated with diverse cellular activities (AAA) ATPase and to evaluate its potential to be a therapeutic target in human disease.
Biological target:
DBeQ is a selective, potent, reversible, and ATP-competitive p97 inhibitor, with an IC50 value of 1.5 μM and 1.6 μM for p97(wt) and p97(C522A), respectively; DBeQ also inhibits Vps4 with an IC50 of 11.5 μM.
In vitro activity:
10 μM DBeQ rapidly promoted activation of the “executioner” caspases-3 and -7 in HeLa cells (Fig. 4A). DBeQ was benchmarked by comparing it with the well-characterized apoptosis inducer staurosporine (STS) and the procaspases-3 and -6 activator 1541. STS induces executioner caspases-3, -6, and -7 via both caspases-8 and -9 in the apoptotic pathway. DBeQ activated caspases-3 and -7 by twofold within 2 h (Fig. 4B) but did not activate caspase-6 after 6 h (Fig. 4C). The impact of DBeQ on initiator caspases-8 and -9 was next evaluated. DBeQ activated the intrinsic caspase-9 apoptotic pathway more than the extrinsic caspase-8 pathway, whereas STS activated both pathways to a similar extent (Fig. 4 D and E). DBeQ was blocked by the general caspase inhibitor [Z-VAD(OMe)FMK; Fig. 4G], whereas accumulation of LC3-II was not affected (Fig. 3D, lane 3), suggesting that the block in autophagosome maturation induced by DBeQ was not an indirect consequence of caspase activation. DBeQ potently inhibits cancer cell growth and is more rapid than a proteasome inhibitor at mobilizing the executioner caspases-3 and -7. The results provide a rationale for targeting p97 in cancer therapy. Reference: Proc Natl Acad Sci U S A. 2011 Mar 22; 108(12): 4834–4839. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064330/
In vivo activity:
To further corroborate our mechanistic study of p97 regulation of the p100 processing, we developed LPS-induced lung pathology model in mock mice and p97-KD mice by intraperitoneal injection of LPS (20 mg/kg) every day (Fig. 5A). As shown in Fig. 5D, DBeQ treatment substantially blocked the processing of p100 into p52, again supporting the notion that p97 facilitates the partial degradation of p100. Consistently, such catalytic inhibition of p97 dramatically down-regulated the transcription of NFKB2 (Fig. 5E). Reference: J Biol Chem. 2015 Aug 7; 290(32): 19558–19568. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528123/
Solvent mg/mL mM
Solubility
DMSO 41.0 120.44
Ethanol 3.2 9.40
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 340.43 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.

Recalculate based on batch purity %
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:
1. Chou TF, Brown SJ, Minond D, Nordin BE, Li K, Jones AC, Chase P, Porubsky PR, Stoltz BM, Schoenen FJ, Patricelli MP, Hodder P, Rosen H, Deshaies RJ. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9. doi: 10.1073/pnas.1015312108. Epub 2011 Mar 7. PMID: 21383145; PMCID: PMC3064330. 2. Nabhan JF, Gooch RL, Piatnitski Chekler EL, Pierce B, Bulawa CE. Perturbation of cellular proteostasis networks identifies pathways that modulate precursor and intermediate but not mature levels of frataxin. Sci Rep. 2015 Dec 16;5:18251. doi: 10.1038/srep18251. PMID: 26671574; PMCID: PMC4680912. 3. Zhang Z, Wang Y, Li C, Shi Z, Hao Q, Wang W, Song X, Zhao Y, Jiao S, Zhou Z. The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100. J Biol Chem. 2015 Aug 7;290(32):19558-68. doi: 10.1074/jbc.M114.630061. Epub 2015 Jun 25. PMID: 26112410; PMCID: PMC4528123.
In vitro protocol:
1. Chou TF, Brown SJ, Minond D, Nordin BE, Li K, Jones AC, Chase P, Porubsky PR, Stoltz BM, Schoenen FJ, Patricelli MP, Hodder P, Rosen H, Deshaies RJ. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9. doi: 10.1073/pnas.1015312108. Epub 2011 Mar 7. PMID: 21383145; PMCID: PMC3064330. 2. Nabhan JF, Gooch RL, Piatnitski Chekler EL, Pierce B, Bulawa CE. Perturbation of cellular proteostasis networks identifies pathways that modulate precursor and intermediate but not mature levels of frataxin. Sci Rep. 2015 Dec 16;5:18251. doi: 10.1038/srep18251. PMID: 26671574; PMCID: PMC4680912.
In vivo protocol:
1. Zhang Z, Wang Y, Li C, Shi Z, Hao Q, Wang W, Song X, Zhao Y, Jiao S, Zhou Z. The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100. J Biol Chem. 2015 Aug 7;290(32):19558-68. doi: 10.1074/jbc.M114.630061. Epub 2015 Jun 25. PMID: 26112410; PMCID: PMC4528123.
1: Bosque A, Dietz L, Gallego-Lleyda A, Sanclemente M, Iturralde M, Naval J, Alava MA, Martínez-Lostao L, Thierse HJ, Anel A. Comparative proteomics of exosomes secreted by tumoral Jurkat T cells and normal human T cell blasts unravels a potential tumorigenic role for valosin-containing protein. Oncotarget. 2016 Apr 11. doi: 10.18632/oncotarget.8678. [Epub ahead of print] PubMed PMID: 27086912. 2: Zhang Y, Li W, Chu M, Chen H, Yu H, Fang C, Sun N, Wang Q, Luo T, Luo K, She X, Zhang M, Yang D. The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ. Mycopathologia. 2016 Jun;181(5-6):329-39. doi: 10.1007/s11046-015-9979-x. Epub 2015 Dec 23. PubMed PMID: 26700222. 3: Nabhan JF, Gooch RL, Piatnitski Chekler EL, Pierce B, Bulawa CE. Perturbation of cellular proteostasis networks identifies pathways that modulate precursor and intermediate but not mature levels of frataxin. Sci Rep. 2015 Dec 16;5:18251. doi: 10.1038/srep18251. PubMed PMID: 26671574; PubMed Central PMCID: PMC4680912. 4: Zhang Z, Wang Y, Li C, Shi Z, Hao Q, Wang W, Song X, Zhao Y, Jiao S, Zhou Z. The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100. J Biol Chem. 2015 Aug 7;290(32):19558-68. doi: 10.1074/jbc.M114.630061. Epub 2015 Jun 25. PubMed PMID: 26112410; PubMed Central PMCID: PMC4528123. 5: Fang CJ, Gui L, Zhang X, Moen DR, Li K, Frankowski KJ, Lin HJ, Schoenen FJ, Chou TF. Evaluating p97 inhibitor analogues for their domain selectivity and potency against the p97-p47 complex. ChemMedChem. 2015 Jan;10(1):52-6. doi: 10.1002/cmdc.201402420. Epub 2014 Nov 6. PubMed PMID: 25377500; PubMed Central PMCID: PMC4280364. 6: Chou TF, Bulfer SL, Weihl CC, Li K, Lis LG, Walters MA, Schoenen FJ, Lin HJ, Deshaies RJ, Arkin MR. Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains. J Mol Biol. 2014 Jul 29;426(15):2886-99. doi: 10.1016/j.jmb.2014.05.022. Epub 2014 May 27. PubMed PMID: 24878061; PubMed Central PMCID: PMC4102644. 7: Auner HW, Moody AM, Ward TH, Kraus M, Milan E, May P, Chaidos A, Driessen C, Cenci S, Dazzi F, Rahemtulla A, Apperley JF, Karadimitris A, Dillon N. Combined inhibition of p97 and the proteasome causes lethal disruption of the secretory apparatus in multiple myeloma cells. PLoS One. 2013 Sep 17;8(9):e74415. doi: 10.1371/journal.pone.0074415. eCollection 2013. PubMed PMID: 24069311; PubMed Central PMCID: PMC3775786. 8: Yi P, Higa A, Taouji S, Bexiga MG, Marza E, Arma D, Castain C, Le Bail B, Simpson JC, Rosenbaum J, Balabaud C, Bioulac-Sage P, Blanc JF, Chevet E. Sorafenib-mediated targeting of the AAA⁺ ATPase p97/VCP leads to disruption of the secretory pathway, endoplasmic reticulum stress, and hepatocellular cancer cell death. Mol Cancer Ther. 2012 Dec;11(12):2610-20. doi: 10.1158/1535-7163.MCT-12-0516. Epub 2012 Oct 5. PubMed PMID: 23041544. 9: Chou TF, Deshaies RJ. Development of p97 AAA ATPase inhibitors. Autophagy. 2011 Sep;7(9):1091-2. Epub 2011 Sep 1. PubMed PMID: 21606684; PubMed Central PMCID: PMC3210319. 10: Chou TF, Brown SJ, Minond D, Nordin BE, Li K, Jones AC, Chase P, Porubsky PR, Stoltz BM, Schoenen FJ, Patricelli MP, Hodder P, Rosen H, Deshaies RJ. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9. doi: 10.1073/pnas.1015312108. Epub 2011 Mar 7. PubMed PMID: 21383145; PubMed Central PMCID: PMC3064330.