Last update 05 Dec 2024
CFTX-1554
Last update 05 Dec 2024
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms AT2R Antagonist (Lilly), CFTX 1554, CFTX-1554 |
Target |
Mechanism AT2R antagonists(Angiotensin II receptor type 2 antagonists) |
Therapeutic Areas |
Active Indication |
Inactive Indication- |
Originator Organization  Confo Therapeutics NVStartup |
Active Organization |
Inactive Organization- |
Drug Highest PhasePhase 1 |
First Approval Date- |
Regulation- |
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Related
2
Clinical Trials associated with CFTX-1554A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of CFTX-1554 in Healthy Subjects, With Comparison of Intake of CFTX-1554 as Liquid Formulation and as Capsule, and After a High-fat Breakfast Versus Fasted
A randomized, double-blind, placebo-controlled study of the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of CFTX-1554 in healthy subjects, with comparison of intake of CFTX-1554 as liquid formulation and as capsule, and after a high-fat breakfast versus fasted. - SAD / MAD/ FE HV
100 Clinical Results associated with CFTX-1554
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100 Translational Medicine associated with CFTX-1554
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100 Patents (Medical) associated with CFTX-1554
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7
Literatures (Medical) associated with CFTX-155401 May 2022FASEB JOURNAL
Sexually dimorphic role of smooth muscle cell estrogen receptor alpha in aging‐associated arterial stiffness
Article
Author: DuPont, Jennifer ; Vorn, Jennifer ; Duffy, Colleen ; Lu, Qing ; Martin, Gregory ; Hill, Michael
Background:
Aging is associated with rising arterial stiffness (AS), an independent risk factor for cardiovascular disease. The development of aging‐associated AS follows a sexually dimorphic pattern with women developing AS later in life. Estrogen and estrogen receptor alpha (ERα) are protective in the premenopausal state, potentially due to the regulation of the vasoprotective angiotensin II type 2 receptor (AT2R), however, the role of estrogen/ERα in aging‐associated AS has not been defined and the mechanisms of the sexually‐dimorphic development of aging‐associated AS are unknown.
Methods/Results:
All studies were conducted in accordance with the FASEB Statement of Principles for the use of Animals in Research and Education. We generated novel smooth muscle cell‐specific ERα‐KO mice and measured aortic pulse wave velocity (PWV), an index of AS, in 3, 12, and 18 month old male and female intact and KO mice. Male mice develop increases in AS from 3 to 12 months compared to 3 to 18 months in females (p<0.05). SMC‐ERα‐KO protected females from the aging‐associated increase in AS (p<0.05). Circulating estrogens also declined in 18 month old females vs. 3 mo. (p<0.05), suggesting a role for unliganded SMC‐ERα in aging‐associated AS. SMC‐ERα‐KO females were also protected from the aging‐associated decline in aortic AT2R expression observed in intact females (p<0.05). To further investigate the potential role of unliganded SMC‐ERα in AS, we performed ovariectomy (OVX) or sham surgeries in young female SMC‐ERα‐Intact and KO mice and measured PWV. Results demonstrated an OVX‐driven increase in AS that was prevented by SMC‐ERα‐KO (p<0.05). This was also associated with an OVX‐mediated decrease in aortic expression of the AT2R, which was prevented by SMC‐ERα‐KO. To determine the in vivo role of AT2R in the vascular protection observed in 12 month old female mice, we treated 12 month old male and female mice with AT2R antagonist PD‐123319 (3mg/kg/day) or vehicle via osmotic minipumps for 4 weeks. Chronic inhibition of the AT2R increased AS in 12 month old females (p<0.05), but not males, suggesting that AT2R‐mediated protection contributes to the delay in aging‐associated AS in female mice. In vitro studies also demonstrated that estrogen upregulates AT2R mRNA and protein in female mouse aortic SMC, supporting an estrogen‐mediated mechanism of AT2R driven vascular protection in females.
Conclusion:
These data indicate sex differences in the time course of the development of aging‐associated arterial stiffness and suggest the presence of unliganded SMC‐ERα contributes specifically to aging‐associated arterial stiffness in females via reductions in vascular AT2R. Further, these results implicate that AT2R agonist therapy may improve cardiovascular outcomes in aging women to retain the beneficial downstream effects of estrogen signaling, without the potential detrimental effects of hormone replacement therapy.
01 May 2022FASEB JOURNAL
Angiotensin AT2 Receptor Activation during Ischemic Injury Protects against High Salt‐Induced Hypertension and Proteinuria in the Long‐term: Role of IL‐17A Cells
Article
Author: Patel, Sanket ; Hussain, Tahir ; Ali, Riyasat
Short time renal ischemia/reperfusion (I/R) causes reversible acute kidney injury (AKI) that often recovers within 5‐7 days. However, a single event of AKI predisposes and makes kidneys susceptible to develop chronic kidney disease (CKD) in conditions such as obesity and hypertension. Recently we have shown that angiotensin type 2 receptor (AT2R) activation by the agonist compound C21 (C21) protects against I/R‐induced AKI in the early injury phase in terms of suppressing pro‐inflammatory cytokines and improving functional injury markers such as reducing proteinuria and blood urea nitrogen (BUN). The late recovery phase (day 5) in the I/R and I/R treated with C21 remained same i.e., the C21 treated and un‐treated animals fully recovered functionally to the same extent but with higher anti‐inflammatory IL‐10 producing and protective Treg cell (FoxP3+) in I/R+C21 compared I/R groups. However, the long‐term protective effect of the AT2R agonist C21 on these recovered kidneys against chronic injury is unknown. To address this question, male Sprague‐Dawley (SD) rats were administered C21 (0.3 mg/kg, i.p.) prior to 30‐minute bilateral renal ischemia and allowed to recover for 5 days, with daily C21 treatment (I/R+ C21), without treatment (I/R) and sham control. On 7th day, all the three groups were placed on high salt (1% NaCl) in drinking water for two weeks but without C21 treatment. On day 6 (prior to initiating high salt treatment), week 1 and 2 of the high salt treatment, renal function parameters (proteinuria), and T cells were quantitated in the blood and kidney (only at 2 weeks). On 6th day, all the three groups showed similar level of proteinuria, suggesting same renal function. However, at week 1 and 2, I/R group had significantly greater proteinuria, suggesting a function injury. Similarly, I/R group showed higher mean arterial blood pressure at two weeks compared with the I/R+C21 and sham control. Consistent to the higher proteinuria and blood pressure in I/R group, there were higher infiltrating proinflammatory (IL‐17A) cells in the kidney in I/R group compared with sham control and I/R+C21 groups. Also, kidney infiltrating CD45 cells, T cells and CD4 T cells were found to be similar among all the groups. Overall, the data indicate that I/R pre‐disposes the kidneys to high salt‐induced chronic injury which is completely prevented by AT2R agonist treatment during AKI phase. Moreover, AT2R’s protective effect could be related to preventing the T cell modulation into proinflammatory IL‐17A cells.
01 Sep 2014EndocrinologyQ2 · MEDICINE
Angiotensin II Type 2 Receptor Stimulation Improves Fatty Acid Ovarian Uptake and Hyperandrogenemia in an Obese Rat Model of Polycystic Ovary Syndrome
Q2 · MEDICINE
Article
Author: Vine, Donna F. ; Noll, Christophe ; Hallberg, Anders ; Gallo-Payet, Nicole ; Carpentier, André C. ; Battista, Marie-Claude ; Baillargeon, Jean-Patrice ; Leblanc, Samuel
Abstract:
Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenism but is also characterized by insulin resistance (IR). Studies showed that overexposure of nonadipose tissues to nonesterified fatty acids (NEFA) may explain both IR and hyperandrogenism. Recent studies indicate that treatment with an angiotensin II type 2 receptor (AT2R)-selective agonist improves diet-induced IR. We thus hypothesized that PCOS hyperandrogenism is triggered by ovarian NEFA overexposure and is improved after treatment with an AT2R agonist. Experiments were conducted in 12-week-old female JCR:LA-cp/cp rats, which are characterized by visceral obesity, IR, hyperandrogenism, and polycystic ovaries. Control JCR:LA +/? rats have a normal phenotype. Rats were treated for 8 days with saline or the selective AT2R agonist C21/M24 and then assessed for: 1) fasting testosterone, NEFA, and insulin levels; and 2) an iv 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid test to determine NEFA ovarian tissue uptake (Km). Compared with controls, saline-treated PCOS/cp rats displayed higher insulin (100 vs 5.6 μU/mL), testosterone (0.12 vs 0.04 nmol/L), NEFA (0.98 vs 0.48 mmol/L), and Km (20.7 vs 12.9 nmol/g·min) (all P < .0001). In PCOS/cp rats, C21/M24 did not significantly improve insulin or NEFA but normalized testosterone (P = .004) and Km (P = .009), which were strongly correlated together in all PCOS/cp rats (ρ = 0.74, P = .009). In conclusion, in an obese PCOS rat model, ovarian NEFA uptake and testosterone levels are strongly associated and are both significantly reduced after short-term C21/M24 therapy. These findings provide new information on the role of NEFA in PCOS hyperandrogenemia and suggest a potential role for AT2R agonists in the treatment of PCOS.
15
News (Medical) associated with CFTX-155411 Nov 2024
Phase 2Phase 3Drug Approval
30 Mar 2023
100 Deals associated with CFTX-1554
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R&D Status
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| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Neuralgia | Phase 1 | NL |  Confo Therapeutics NVStartup | 10 Mar 2022 |
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