Delving into the Latest Updates on ADH-10001 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Exherin

+ [1]

Target

CDH2

Action

inhibitors

Mechanism

CDH2 inhibitors(Cadherin-2 inhibitors), Angiogenesis inhibitors

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesDigestive System Disorders+ [2]

Active Indication-

Inactive Indication

Carcinoma of ampulla of VaterGallbladder adenocarcinomaIntrahepatic Cholangiocarcinoma+ [4]

Originator Organization

McGill-Queen's University Press

Active Organization-

Inactive Organization

Fennec Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H34N8O6S2

InChIKeyFQVLRGLGWNWPSS-BXBUPLCLSA-N

CAS Registry229971-81-7

Sequence Code 33854749

This phase I trial studies the side effects and best dose of ADH-1 when given together with gemcitabine hydrochloride and cisplatin in treating patients with pancreatic or biliary tract cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or spread to other parts of the body (metastatic) and cannot be removed by surgery. ADH-1 may stop the growth of cancer cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ADH-1 together with gemcitabine hydrochloride and cisplatin may kill more tumor cells.

Start Date09 Apr 2013

Sponsor / Collaborator

University of Nebraska

[+2]

NCT00421811

/ CompletedPhase 1/2

An Open-Label, Multicenter, Phase 1/2 Dose Escalation Study to Evaluate Safety, Tolerability and Anti-tumor Activity of Systemic ADH-1 in Combination With Normothermic Isolated Limb Infusion of Melphalan in Subjects With Locally Advanced In-Transit Malignant Melanoma (Adherex Protocol Number AHX-01-007).

N-cadherin, a protein involved in blood vessel cell binding and on the surface of many tumor cells, is increased as cancer progresses. ADH-1 blocks N-cadherin. This study will test the safety and effects of the combination ADH-1 with Normothermic Isolated Limb Infusion of Melphalan in subjects with locally advanced malignant melanoma.

Start Date01 Apr 2007

Sponsor / Collaborator

Fennec Pharmaceuticals, Inc.

NCT00390676

/ CompletedPhase 1

A Phase 1, Multicenter, Dose-Escalation Study to Investigate the Safety and Tolerability of ADH-1 in Combination With 1) Carboplatin or 2) Docetaxel or 3) Capecitabine in Subjects With N-Cadherin Positive, Advanced Solid Tumors (Adherex Protocol Number AHX-01-006)

N-cadherin, a protein involved in blood vessel cell binding, is increased as cancer progresses, and is on the surface of many tumor cells. ADH-1 blocks N-cadherin. This study will test the safety and effects of the combination ADH-1 and carboplatin or ADH-1 and docetaxel or ADH-1 and capecitabine in subjects with specific incurable, solid tumors with a protein biomarker called N-cadherin.

Start Date01 Nov 2006

Sponsor / Collaborator

Fennec Pharmaceuticals, Inc.

[+1]

100 Clinical Results associated with ADH-10001

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100 Translational Medicine associated with ADH-10001

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100 Patents (Medical) associated with ADH-10001

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110

Literatures (Medical) associated with ADH-10001

01 Feb 2023·iScience

Low-dose ethanol increases aflatoxin production due to the adh1-dependent incorporation of ethanol into aflatoxin biosynthesis

Article

Author: Kushiro, Masayo ; Sakuda, Shohei ; Nakagawa, Hiroyuki ; Enomoto, Hirofumi ; Furukawa, Tomohiro

Aflatoxins are toxic secondary metabolites produced by some aspergilli, including Aspergillus flavus. Recently, ethanol has attracted attention as an agent for the control of aflatoxin contamination. However, as aflatoxin biosynthesis utilizes acetyl coenzyme A, ethanol may be conversely exploited for aflatoxin production. Here, we demonstrated that not only the ¹³C of labeled ethanol, but also that of labeled 2-propanol, was incorporated into aflatoxin B₁ and B₂, and that ethanol and 2-propanol upregulated aflatoxin production at low concentrations (<1% and <0.6%, respectively). In the alcohol dehydrogenase gene adh1 deletion mutant, the ¹³C incorporation of labeled ethanol, but not labeled 2-propanol, into aflatoxin B₁ and B₂ was attenuated, indicating that the alcohols have different utilization pathways. Our results show that A. flavus utilizes ethanol and 2-propanol as carbon sources for aflatoxin biosynthesis and that adh1 indirectly controls aflatoxin production by balancing ethanol production and catabolism.

02 Jan 2023·Molecular and Cellular Biology

Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast

Article

Author: Burke, Giovanni L. ; McNeil, J. Bryan ; Akhter, Akhi ; Baig, Mohammad S. ; Bergey, Benjamin G. ; Rosonina, Emanuel ; Babu, John ; Moallem, Marjan

Numerous proteins are sumoylated in normally growing yeast and SUMO conjugation levels rise upon exposure to several stress conditions. We observe high levels of sumoylation also during early exponential growth and when nutrient-rich medium is used. However, we find that reduced sumoylation (∼75% less than normal) is remarkably well-tolerated, with no apparent growth defects under nonstress conditions or under osmotic, oxidative, or ethanol stresses. In contrast, strains with reduced activity of Ubc9, the sole SUMO conjugase, are temperature-sensitive, implicating sumoylation in the heat stress response, specifically. Aligned with this, a mild heat shock triggers increased sumoylation which requires functional levels of Ubc9, but likely also depends on decreased desumoylation, since heat shock reduces protein levels of Ulp1, the major SUMO protease. Furthermore, we find that a ubc9 mutant strain with only ∼5% of normal sumoylation levels shows a modest growth defect, has abnormal genomic distribution of RNA polymerase II (RNAPII), and displays a greatly expanded redistribution of RNAPII after heat shock. Together, our data implies that SUMO conjugations are largely dispensable under normal conditions, but a threshold level of Ubc9 activity is needed to maintain transcriptional control and to modulate the redistribution of RNAPII and promote survival when temperatures rise.

01 Jan 2023·Frontiers in oncology

[¹⁸F]AlF-NOTA-ADH-1: A new PET molecular radiotracer for imaging of N-cadherin-positive tumors.

Article

Author: Alhaskawi, Ahmad ; Wen, Guanghua ; Liu, Zhenfeng ; Huang, Yuqiao ; Zhou, Haiying ; Ye, Qianni ; Wang, GuoLin ; Wang, Zewei ; Dong, Mengjie ; Zhang, Shuyi ; Lu, Hui ; Dong, Yanzhao

BackgroundThe cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers.MethodsIn this study, [¹⁸F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo.ResultsRadiolabeling of ADH-1 with [¹⁸F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of >97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [¹⁸F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor.Conclusion[¹⁸F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [¹⁸F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.

100 Deals associated with ADH-10001

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External Link

KEGG	Wiki	ATC	Drug Bank
-	ADH-10001	-	DB05485

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Carcinoma of ampulla of Vater	Phase 2	United States	Fennec Pharmaceuticals, Inc.	09 Apr 2013
Gallbladder adenocarcinoma	Phase 2	United States	Fennec Pharmaceuticals, Inc.	09 Apr 2013
Intrahepatic Cholangiocarcinoma	Phase 2	United States	Fennec Pharmaceuticals, Inc.	09 Apr 2013
Klatskin Tumor	Phase 2	United States	Fennec Pharmaceuticals, Inc.	09 Apr 2013
Pancreatic adenocarcinoma metastatic	Phase 2	United States	Fennec Pharmaceuticals, Inc.	09 Apr 2013
Locally Advanced Melanoma	Phase 2	United States	Fennec Pharmaceuticals, Inc.	01 Apr 2007
Solid tumor	Phase 2	Switzerland	Fennec Pharmaceuticals, Inc.	01 Jun 2005
Solid tumor	Phase 2	Italy	Fennec Pharmaceuticals, Inc.	01 Jun 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01825603 (ASCO_GI2017)	Phase 1	Biliary Tract Neoplasms \| Pancreatic Cancer	17	ADH-1	(gjcjodpdji) = gkunqufehu yoylzbklbn (rpuepdmete ) View more	-	21 Mar 2017
ASCO2008	Phase 1	Solid tumor	35	ADH-1	(ojdiaxojzu) = pgtlmuxqlw deceothfcm (lwnpdirvnn )	-	20 May 2008
ASCO2008	Phase 1	Solid tumor	35	Docetaxel	nqwavozsde(cnswpyyatd) = tswpqhzmxg ulcdejdlhv (ugqyqrxbxe )	-	20 May 2008
ASCO2008	Phase 1/2	Locally Advanced Melanoma	11	Systemic ADH-1	ldbwniofyy(edncwfxooj) = kyaobmlyxq awbfxzackw (rajjmmfyxo )	-	20 May 2008
ASCO2007	Phase 2	Solid tumor	-	ADH-1 500 mg/m2 q 3 W	kbxxdtidsk(jpkcopltin) = ccvxznjffi kpaegxajyh (afvnfeidca ) View more	-	20 Jun 2007
ASCO2007	Phase 2	Solid tumor	-	ADH-1 600 mg/m2 qW	kbxxdtidsk(jpkcopltin) = rssadkxixu kpaegxajyh (afvnfeidca ) View more	-	20 Jun 2007
ASCO2005	Phase 1	Solid tumor	33	ADH-1	(hybtyzrtmt) = xfsuysjgpb oqjvxzfagc (lddrajssjq )	Positive	01 Jun 2005

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Translational Medicine

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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ADH-10001

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation