Delving into the Latest Updates on ADH-10001 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Exherin

+ [1]

Target

CDH2

Mechanism

CDH2 inhibitors(Cadherin-2 inhibitors), Angiogenesis inhibitors

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

MelanomaNeoplasmsSolid tumor

Originator Organization

McGill-Queen's University Press

Active Organization-

Inactive Organization

Fennec Pharmaceuticals, Inc.McGill-Queen's University Press

AstraZeneca Pharmaceuticals Co. Ltd.

+ [1]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC22H34N8O6S2

InChIKeyFQVLRGLGWNWPSS-BXBUPLCLSA-N

CAS Registry229971-81-7

Gene Sequence

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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20

Literatures (Medical) associated with ADH-10001

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 ; Dong, Yanzhao ; Lu, Hui ; Zhang, Shuyi

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.

01 Aug 2022·Cell Reports Medicine

hiPSC-derived bone marrow milieu identifies a clinically actionable driver of niche-mediated treatment resistance in leukemia

Article

Author: Nizami, Salem ; Schwab, Claire ; McNeill, Hesta ; Nelson, Ryan ; Hockney, Sean ; Allan, James M ; Coxhead, Jonathan ; Angel, Sharon H ; Wilson, Aaron ; Beckett, Melanie ; Halsey, Christina ; Moorman, Anthony V ; Blair, Helen ; Vormoor, Josef ; Zhou, Peixun ; Heidenreich, Olaf ; Nakjang, Sirintra ; Russell, Lisa J ; Pal, Deepali ; Sinclair, Paul ; Tirtakusuma, Ricky ; Parker, Jessica ; Singh, Mankaran ; Harrison, Christine J

Leukemia cells re-program their microenvironment to augment blast proliferation and enhance treatment resistance. Means of clinically targeting such niche-driven treatment resistance remain ambiguous. We develop human induced pluripotent stem cell (hiPSC)-engineered niches to reveal druggable cancer-niche dependencies. We reveal that mesenchymal (iMSC) and vascular niche-like (iANG) hiPSC-derived cells support ex vivo proliferation of patient-derived leukemia cells, affect dormancy, and mediate treatment resistance. iMSCs protect dormant and cycling blasts against dexamethasone, while iANGs protect only dormant blasts. Leukemia proliferation and protection from dexamethasone-induced apoptosis is dependent on cancer-niche interactions mediated by CDH2. Consequently, we test CDH2 antagonist ADH-1 (previously in Phase I/II trials for solid tumors) in a very aggressive patient-derived xenograft leukemia mouse model. ADH-1 shows high in vivo efficacy; ADH-1/dexamethasone combination is superior to dexamethasone alone, with no ADH-1-conferred additional toxicity. These findings provide a proof-of-concept starting point to develop improved, potentially safer therapeutics targeting niche-mediated cancer dependencies in blood cancers.

01 Apr 2022·Journal of Cellular and Molecular Medicine

Telmisartan anti‐cancer activities mechanism through targeting N‐cadherin by mimicking ADH‐1 function

Article

Author: Ghasemi, Younes ; Mostafavi‐Pour, Zohreh ; Khajeh, Sahar ; Razban, Vahid ; Khorsand, Marjan ; Nezafat, Navid ; Eslami, Mahboobeh

AbstractThis study aimed to investigate if Telmisartan as a novel N‐cadherin antagonist, can overcome cell migration of cancer cells. We investigated the mechanism and influence of Docetaxel and Telmisartan (as an analogous to ADH‐1, which is a well‐known N‐cadherin antagonist) on cancer cells. The effect of ADH‐1 and Telmisartan on cell attachment in PC3, DU145, MDA‐MB‐468 cell lines using recombinant human N‐cadherin was studied. Cell viability assay was performed to examine the anti‐proliferative effects of Telmisartan, ADH‐1 and Docetaxel. Migration was examined via wound healing assay, and apoptosis was determined by flow cytometry. The expression of AKT‐1 as a downstream gene of N‐cadherin signalling pathway was assayed by real‐time PCR. Treatment of PC3, MDA‐MB‐468 and DU145 cells with Telmisartan (0.1 µM) and ADH‐1 (40 µM) resulted in 50%, 58% and approximately 20% reduction in cell attachment to N‐cadherin coated plate respectively. It shows reduction of cell attachment in PC3 and MDA‐MB‐468 cell lines appeared to be more sensitive than that of DU145 cells to the Telmisartan and ADH‐1 treatments. Telmisartan (0.1 µM) and Docetaxel (0.01 nM) significantly reduced cell migration in PC3 and MDA‐MB‐468 cell lines compared with the control group. Using Real‐time PCR, we found that Telmisartan, Docetaxel and ADH‐1 had significant influence on the AKT‐1 mRNA level. The results of the current study for the first time suggest that, Telmisartan, exerts anti‐proliferation and anti‐migration effects by targeting antagonistically N‐cadherin. Also, these data suggest that Telmisartan as a less expensive alternative to ADH‐1 could potentiate Docetaxel anticancer effects.

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
Neoplasms	Phase 2	US	Fennec Pharmaceuticals, Inc.	13 Dec 2005
Neoplasms	Phase 2	CA	Fennec Pharmaceuticals, Inc.	13 Dec 2005
Melanoma	Phase 2	-	AstraZeneca Pharmaceuticals Co. Ltd.	-
Melanoma	Phase 2	US	Fennec Pharmaceuticals, Inc.	-
Melanoma	Phase 2	-	McGill-Queen's University Press	-
Melanoma	Phase 2	-	National Cancer Institute	-
Solid tumor	Phase 2	CA	Fennec Pharmaceuticals, Inc.	-
Solid tumor	Phase 2	IT	Fennec Pharmaceuticals, Inc.	-
Solid tumor	Phase 2	CH	Fennec Pharmaceuticals, Inc.	-

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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	(vttpwitpvx) = rbzggszcry tiahtaxutk (evpholocko ) View more	-	21 Mar 2017
ASCO2008	Phase 1/2	Locally Advanced Melanoma	11	Systemic ADH-1	hrdxehvjae(zspzwzujrf) = mydppjieab jlswgbrbse (ttzymiaqvo )	-	20 May 2008
ASCO2008	Phase 1	Solid tumor	35	ADH-1	(simwhzxutq) = eibhmhjxyt lvumphvsdo (likibhkgbu )	-	20 May 2008
ASCO2008	Phase 1	Solid tumor	35	Docetaxel	chraavjxbt(olnpqoxusm) = cibenezlhu eyflmhpszu (irtkjhbllh )	-	20 May 2008
ASCO2007	Phase 2	Solid tumor	-	ADH-1 500 mg/m2 q 3 W	rdzmwyoilk(bttfzdcoih) = jgofjzuzvc cketbaioyd (uqfvifpvjo ) View more	-	20 Jun 2007
ASCO2007	Phase 2	Solid tumor	-	ADH-1 600 mg/m2 qW	rdzmwyoilk(bttfzdcoih) = kyfbvzvcvm cketbaioyd (uqfvifpvjo ) View more	-	20 Jun 2007
ASCO2005	Phase 1	Solid tumor	33	ADH-1	(ueuwdirqwm) = lveigeyegk xvgpqqkdyv (ufhmrptnxr )	Positive	01 Jun 2005