Dibenzazepine | Iminostilbene | YO-01027 | CAS#209984-56-5 | gamma-Secretase Inhibitor

MedKoo Cat#: 407112 | Name: Dibenzazepine

Description:

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

Dibenzazepine, also known as YO-01027 and Iminostilbene, is a potent γ-secretase inhibitor. Dibenzazepine also potently blocks amyloid precursor protein-like (APPL) and Notch cleavage. γ-Secretase is a fascinating, multi-subunit, intramembrane cleaving protease that is now being considered as a therapeutic target for a number of diseases. Potent, orally bioavailable γ-secretase inhibitors (GSIs) have been developed and tested in humans with Alzheimer's disease (AD) and cancer.

Chemical Structure

Dibenzazepine

CAS#209984-56-5

Theoretical Analysis

MedKoo Cat#: 407112

Name: Dibenzazepine

CAS#: 209984-56-5

Chemical Formula: C26H23F2N3O3

Exact Mass: 463.1708

Molecular Weight: 463.48

Elemental Analysis: C, 67.38; H, 5.00; F, 8.20; N, 9.07; O, 10.36

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 230.00	Ready to ship
50mg	USD 400.00	Ready to ship
100mg	USD 700.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship

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Related CAS #

No Data

Synonym

YO-01027; YO 01027; YO01027; Dibenzazepine; DBZ; Iminostilbene; Deshydroxy LY-411575.

IUPAC/Chemical Name

(S)-2-(2-(3,5-difluorophenyl)acetamido)-N-((S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)propanamide

InChi Key

QSHGISMANBKLQL-OWJWWREXSA-N

InChi Code

InChI=1S/C26H23F2N3O3/c1-15(29-23(32)13-16-11-17(27)14-18(28)12-16)25(33)30-24-21-9-4-3-7-19(21)20-8-5-6-10-22(20)31(2)26(24)34/h3-12,14-15,24H,13H2,1-2H3,(H,29,32)(H,30,33)/t15-,24-/m0/s1

SMILES Code

C[C@H](NC(CC1=CC(F)=CC(F)=C1)=O)C(N[C@@H]2C(N(C)C3=CC=CC=C3C4=CC=CC=C24)=O)=O

Appearance

Yellow to orange 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# C8R10B12

QC Data

View QC data: current batch, Lot# C8R10B12

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Dibenzazepine is a potent γ-secretase inhibitor with IC50 values of 2.92 and 2.64 nM for Notch and APPL cleavage, respectively.

In vitro activity:

The effect of DBZ (Dibenzazepine) on promoting the proliferation of SCs in cultured mouse cochleae was investigated. Cochleae were harvested from P1 C57/BL6 mice and then cultured in DMEM/F12 media with 5 μM or 10 μM DBZ for 3 days, and 10 μM EdU was added for the entire culture period (Figure 1, Figure S1). No Sox2+/EdU+ cells were observed in the vehicle control group (Figure 1A, Figure S1A, S2A). There were some proliferating SCs as indicated by Sox2+/EdU+ cells in the cochleae treated with 5 μM DBZ, and these were primarily seen in the apical turn with some in the middle turn of the cochlea, while very few were seen in the basal turn (Figure 1B, 1G1, Figure S1B, S2B). In the cochleae treated with 10 μM DBZ, there were significantly more Sox2+/EdU+ SCs in the apical and middle turns, with most of the Sox2+/EdU+ SCs still seen in the apical turn (Figure 1C, G1, Figure S1C, S2C). The total number of SCs increased after the DBZ treatment (Figure 1H1). Reference: Cell Prolif. 2020 Sep; 53(9): e12872. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507434/

In vivo activity:

Notably, the pre-treatment of cisplatin-injected group with DBZ (Dibenzazepine) ameliorated the oxidative stress by significantly increasing GSH and catalase levels and lowering MDA levels in the kidney homogenate. In addition to the oxidative stress, inflammation was proven to play an essential role in the pathogenesis of cisplatin-induced renal injury. In this study, the cisplatin-treated group showed a marked increase in pro-inflammatory cytokines tissue levels; IL-1β and TNF-α. On the other side, DBZ exerted anti-inflammatory effects where the group that received DBZ pre-treatment showed a significant decrease in the kidney contents of the assessed pro-inflammatory markers. Furthermore, the present investigation shows another explanation for the renoprotection effect conferred by DBZ that is linked to the suppression of NF-κB, which was elevated in the cisplatin-injected group. Indeed, the NF-κB plays an important role in various biological processes, including immune response, inflammation, regulation of cell differentiation, proliferation and survival. In current study, cisplatin-treated group showed a marked elevation in NF-κB immune-reactivity. Nevertheless, this was significantly attenuated in the group that received DBZ pre-treatment. Upon investigating the cellular pathways of cisplatin injury to kidney, apoptosis was found to be considerably involved. The results showed that cisplatin injection in rats triggered apoptotic cell death that was represented by significantly enhancing the active form of the executive caspase, caspase-3, in renal tissues. Moreover, the effect of cisplatin on the level of capsase-3 enzyme was notably reduced by DBZ pre-treatment. Reference: Front Pharmacol. 2020; 11: 567852. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768080/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	54.1	116.70

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 463.48 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.

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. Abd El-Rhman RH, El-Naga RN, Gad AM, Tadros MG, Hassaneen SK. Dibenzazepine Attenuates Against Cisplatin-Induced Nephrotoxicity in Rats: Involvement of NOTCH Pathway. Front Pharmacol. 2020 Dec 14;11:567852. doi: 10.3389/fphar.2020.567852. PMID: 33381027; PMCID: PMC7768080. 2. Wu J, Dong X, Li W, Zhao L, Zhou L, Sun S, Li H. Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice. Cell Prolif. 2020 Sep;53(9):e12872. doi: 10.1111/cpr.12872. Epub 2020 Jul 17. PMID: 32677724; PMCID: PMC7507434. 3. 2. Zheng YH, Li FD, Tian C, Ren HL, Du J, Li HH. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One. 2013 Dec 16;8(12):e83310. doi: 10.1371/journal.pone.0083310. PMID: 24358274; PMCID: PMC3865307.

In vitro protocol:

In vivo protocol:

1: Sanabría CM, Palma A, Cobo J, Glidewell C. Three closely related dibenzazepine carboxylic acids: hydrogen-bonded aggregation in one, two and three dimensions. Acta Crystallogr C Struct Chem. 2014 Mar;70(Pt 3):332-7. doi: 10.1107/S2053229614003568. Epub 2014 Feb 22. PubMed PMID: 24594729. 2: Zheng YH, Li FD, Tian C, Ren HL, Du J, Li HH. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One. 2013 Dec 16;8(12):e83310. doi: 10.1371/journal.pone.0083310. eCollection 2013. PubMed PMID: 24358274; PubMed Central PMCID: PMC3865307. 3: Tsoung J, Panteleev J, Tesch M, Lautens M. Multicomponent-multicatalyst reactions (MC)(2)R: efficient dibenzazepine synthesis. Org Lett. 2014 Jan 3;16(1):110-3. doi: 10.1021/ol4030925. Epub 2013 Dec 13. PubMed PMID: 24328339. 4: Al-Tel TH, Al-Qawasmeh RA, Schmidt MF, Al-Aboudi A, Rao SN, Sabri SS, Voelter W. Rational design and synthesis of potent dibenzazepine motifs as beta-secretase inhibitors. J Med Chem. 2009 Oct 22;52(20):6484-8. doi: 10.1021/jm9008482. PubMed PMID: 19788239. 5: Al-Qawasmeh RA, Lee Y, Cao MY, Gu X, Viau S, Lightfoot J, Wright JA, Young AH. 11-Phenyl-[b,e]-dibenzazepine compounds: novel antitumor agents. Bioorg Med Chem Lett. 2009 Jan 1;19(1):104-7. doi: 10.1016/j.bmcl.2008.11.001. Epub 2008 Nov 6. PubMed PMID: 19027297. 6: Syeda A, Mahesh HR, Syed AA. 2,2'-Bipyridine as a new and sensitive spectrophotometric reagent for the determination of nanoamounts of certain dibenzazepine class of tricyclic antidepressant drugs. Farmaco. 2005 Jan;60(1):47-51. Epub 2004 Dec 24. PubMed PMID: 15652369. 7: Dardonville C, Jimeno ML, Alkorta I, Elguero J. Homoheteroaromaticity: the case study of azepine and dibenzazepine. Org Biomol Chem. 2004 Jun 7;2(11):1587-91. Epub 2004 May 11. PubMed PMID: 15162209. 8: Li R, Tränkle C, Mohr K, Holzgrabe U. Hexamethonium-type allosteric modulators of the muscarinic receptors bearing lateral dibenzazepine moieties. Arch Pharm (Weinheim). 2001 Apr;334(4):121-4. PubMed PMID: 11382147. 9: Brusova EG, Likhosherstov AM, Gritsenko AN. [The interaction of dialkylaminoacyl derivatives of phenothiazine, dibenzazepine and dibenzdiazepine with opiate receptors]. Eksp Klin Farmakol. 1996 Mar-Apr;59(2):20-3. Russian. PubMed PMID: 8974557. 10: Bruhwyler J, Liégeois JF, Lejeune C, Rogister F, Delarge J, Géczy J. New dibenzazepine derivatives with disinhibitory and/or antidepressant potential: neurochemical and behavioural study in the open-field and forced swimming tests. Behav Pharmacol. 1995 Dec;6(8):830-838. PubMed PMID: 11224387. 11: Radwańska A, Frackowiak T, Ibrahim H, Aubry AF, Kaliszan R. Chromatographic modelling of interactions between melanin and phenothiazine and dibenzazepine drugs. Biomed Chromatogr. 1995 Sep-Oct;9(5):233-7. PubMed PMID: 8593425. 12: Liégeois JF, Rogister F, Delarge J, Pincemail J. Peroxidase-catalysed oxidation of different dibenzazepine derivatives. Arch Pharm (Weinheim). 1995 Feb;328(2):109-12. PubMed PMID: 7726734. 13: Brusova EG. [Effects of phenothiazine and dibenzazepine derivatives on the muscarinic cholinergic system]. Biull Eksp Biol Med. 1992 Jan;113(1):60-2. Russian. PubMed PMID: 1391868. 14: Hussein SA, El-Kommos ME, Hassan HY, Mohamed AM. Spectrophotometric determination of some dibenzazepine drugs by electrophilic coupling. Talanta. 1989 Sep;36(9):941-4. PubMed PMID: 18964837. 15: Lavoie PA, Tiberi M. Inhibition of fast axonal transport in bullfrog nerves by dibenzazepine and dibenzocycloheptadiene calmodulin inhibitors. J Neurobiol. 1986 Nov;17(6):681-95. PubMed PMID: 2432170. 16: Senova ZP, Lyskovtsev VV, Grigor'eva EK, Gorbunova VV, Kaverina NV. [Anti-arrhythmia and antifibrillatory properties of dibenzazepine derivatives]. Kardiologiia. 1986 Aug;26(8):24-8. Russian. PubMed PMID: 3761845. 17: Berdiaev SIu, Marko R, Kelemen K, Darinskiĭ NV, Kaverina NV. [Electrophysiologic research on the anti-arrhythmia properties of bonnecor--a new dibenzazepine derivative]. Kardiologiia. 1986 Aug;26(8):16-9. Russian. PubMed PMID: 3531669. 18: Mori M, Fujita M, Kozuka H. The effect of phenothiazine and dibenzazepine pretreatment on the metabolism of methamphetamine in rats. J Pharm Pharmacol. 1985 Nov;37(11):819-20. PubMed PMID: 2867166. 19: Oxenkrug GF. Equal inhibitory effect of dimethyl- and monomethyl-beta-aminopropionylic derivatives of dibenzazepine on the uptake of [3H]noradrenaline by rat brain synaptosomes. Biochem Pharmacol. 1979 Mar 15;28(6):938-9. PubMed PMID: 454490. 20: Beyer KH, Wagemann A. [The influence of some carbamazepin metabolites on Nielsen's quantitative determination. 5th communication: on chemistry and analytics of dibenzazepine derivatives (author's transl)]. Arzneimittelforschung. 1978;28(2):246-8. German. PubMed PMID: 580385.