A Phase 1 Study of AR-12 (2-Amino-N-[4-[5-(2 Phenanthrenyl)-3-(Trifluoromethyl)-1H-pyrazol-1-yl] Phenyl]-Acetamide) in Adult Patients With Advanced or Recurrent Solid Tumors or Lymphoma, for Which No Standard Therapy Is Available

The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12 by describing dose-limiting toxicities (DLTs), and thereby establishing the maximum tolerated dose (MTD) or, in the absence of reaching an MTD, a recommended dose (RD) for additional study of oral AR-12 administered daily in cycles of 28 days (28 consecutive days of once daily treatment with at least a 7-day break between the first and second treatment cycles and recovery of toxicity to grade 1 or less, with no planned off-treatment days between subsequent cycles).

Start Date01 Aug 2009

Sponsor / Collaborator

Arno Therapeutics, Inc.

100 Clinical Results associated with AR-12

100 Translational Medicine associated with AR-12

100 Patents (Medical) associated with AR-12

105

Literatures (Medical) associated with AR-12

04 Mar 2024·Cureus

Cryptococcosis and Cryptococcal Meningitis: A Narrative Review and the Up-to-Date Management Approach

Review

Author: Shrivastava, Shitij ; Ghazanfar, Haider ; Fortuzi, Ked ; Hasan, Khushbu Z ; Qureshi, Zaheer A ; Kandhi, Sameer ; Ghazanfar, Ali ; Dileep, Arundhati ; Altaf, Faryal

Cryptococcosis is a fungal infectious disease that enormously impacts human health worldwide. Cryptococcal meningitis is the most severe disease caused by the fungus Cryptococcus, and can lead to death, if left untreated. Many patients develop resistance and progress to death even after treatment. It requires a prolonged treatment course in people with AIDS. This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine. This review also evaluated the management and empiric treatment of cryptococcus meningitis. The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed.

25 Oct 2023·Zhen ci yan jiu = Acupuncture research

Electroacupuncture inhibits PDK1/Akt/HCN4 pathway to improve neurogenic urinary retention in rats.

Article

Author: Zhang, Ren ; Li, Zheng-Fei ; Kuang, Yao ; Zhao, Guo-Rui

OBJECTIVESTo observe the therapeutic effect of electroacupuncture (EA) on neurogenic urinary retention rats, so as to explore the underlying mechanism of EA in treating neurogenic urinary retention by focusing on 3-phosphoinositide-dependent protein kinase 1 (PDK1)/protein kinase B (Akt)/hyperpolarization activated cyclic nucleotide-gated cation channel 4 (HCN4) pathway.METHODSFemale SD rats were randomly divided into sham operation, model, EA, PDK1 inhibitor, HCN4 blocker and EA + HCN4 blocker groups, with 20 rats in each group. The model of sacral spinal cord injury was established by modified Hassan Shaker spinal cord transection method. EA (2 Hz/15 Hz, 0.5 mA) was applied to "Zhongji" (CV3) and "Zhongliao" (BL33) for 20 min, once daily for 10 days. Rats of the PDK1 inhibitor group received intraperitoneal injection of OSU-03012 (20 mg/kg), and rats of the HCN4 blocker group received intraperitoneal injection of ivabradine (10 mg/kg), both once every other day for 10 days. The urodynamic indexes of rats were detected by multi-channel physiological recorder；muscle strip test was used to detect detrusor excitability；the morphological changes of bladder were observed by HE staining. Immunofluorescence double staining was used to detect the co-expression of HCN4 and C-Kit, a specific marker of interstitial cells of Cajal in bladder. Western blot was used to detect the expression of PDK1/Akt/HCN4 pathway proteins in bladder tissue and heat shock protein 27 (HSP27), a protein related to bladder contraction function.RESULTSCompared with the sham operation group, the rats in the model group showed urinary dysfunction, decreased leak point pressure, isolated detrusor spontaneous contraction frequency, fluorescence intensity of C-Kit positive cells, HCN4⁺/C-Kit⁺ co-expression, HCN4 and p-HSP27/HSP27 protein expression in bladder tissue (P<0.05), and increased maximum bladder capacity and comp-liance, minimum tension during contraction of isolated detrusor, PDK1 and p-Akt/Akt protein expression in bladder tissue (P<0.05). Meanwhile, the above index were all reversed after EA and PDK1 inhibitor intervention (P<0.05). In comparison with the EA group, the rats had severe urinary dysfunction, the urine leakage point pressure, spontaneous contraction frequency, fluorescence intensity of C-Kit positive cells, the co-expression of HCN4⁺/C-Kit⁺, and the protein expression of HCN4 and p-HSP27/HSP27 were decreased (P<0.05), the maximum bladder capacity and compliance, the minimum tension during contraction of isolated detrusor, and the protein expression of PDK1 and p-Akt/Akt in bladder tissue were increased (P<0.05) in both HCN4 blocker and EA+HCN4 blocker groups. HE staining showed exfoliated bladder epithelium and disordered layers, vacuolization of bladder wall cells, with infiltration of neutrophils in mucosal and muscular layers in the model group, which were relatively milder in the EA and PDK1 inhibitor groups, but worse in the HCN4 blocker and EA + HCN4 blocker groups.CONCLUSIONSEA can improve the urinary dysfunction in rats with neurogenic urinary retention, which may be related to its effect in inhibiting the activation of PDK1/Akt pathway, promo-ting HCN4-mediated detrusor excitatory contraction and urinary electrical signal activation.

30 Jun 2023·Bioinformation

Molecular docking analysis of MCL-1 inhibitors for breast cancer management

Article

Author: Asif Hussain, Akber ; Hanan Mamdouh, Alotaibi ; Marui, Ibrahim Shafei ; Abdulrahman, Alzahrani ; Mohammed Hadi, Ghawi ; Qamre, Alam ; Mohammad Azhar, Kamal ; Ali Abdullah, Asiri

Myeloid leukemia 1 (MCL-1), a BCL-2 protein family member, acts as an anti-apoptotic protein by interacting with pro-apoptotic BCL-2 proteins. Its overexpression is frequently observed in numerous cancer types including breast cancer, and is closely linked to the initiation and progression of tumors as well as poor prognosis and resistance to therapeutic interventions. Here, a database of 3402 chemicals with established therapeutic activity against various diseases was chosen and systematically screened against the MCL-1 protein. Visual inspection and binding energy analysis revealed that the compounds OSU-03012, Raltitrexed, Ostarine (MK-2866), Dovitinib (TKI-258), and Varespladib (LY315920) had strong binding affinity for the MCL-1 protein. Notably, their binding affinity was higher than that of the control compounds. These compounds exhibited strong interactions with critical amino acid residues of the MCL-1 protein. Furthermore, these compounds shared several common amino acid residue interactions with the control compounds. These findings suggest that these compounds may be useful as MCL-1 inhibitors in the treatment of breast cancer. However, additional experimental validation is required to confirm these findings.

100 Deals associated with AR-12

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoma	Phase 1	US	Arno Therapeutics, Inc.	01 Aug 2009
Lymphoma	Phase 1	GB	Arno Therapeutics, Inc.	01 Aug 2009
Relapsed Solid Neoplasm	Phase 1	US	Arno Therapeutics, Inc.	01 Aug 2009
Relapsed Solid Neoplasm	Phase 1	GB	Arno Therapeutics, Inc.	01 Aug 2009

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00978523 (ASCO2013)	Phase 1	HR-positive/HER2-low Solid Tumors	35	AR-12	(jejjftindz) = G2-1pt ababklophp (hxwhcgddts ) View more	-	20 May 2013

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