APP inhibitors(Beta amyloid A4 protein inhibitors), PKCδ stimulants(Protein kinase C delta stimulants), PKCε stimulants(protein kinase C epsilon stimulants)

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [2]

Active Indication

Acute Lymphoblastic LeukemiaHIV Infections

Inactive Indication

Acinar Cell CarcinomaAcute Promyelocytic LeukemiaAdult acute myeloid leukemia with del(5q)+ [30]

Originator Organization

TAO Synergies, Inc.

Active Organization

Bryologyx, Inc.

Inactive Organization

National Cancer Institute

National Institute on Aging

National Institutes of Health

+ [1]

License Organization

Neurotrope, Inc.

Bryologyx, Inc.

National Cancer Institute

+ [4]

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (United States)

Structure/Sequence

Molecular FormulaC47H68O17

InChIKeyMJQUEDHRCUIRLF-UHFFFAOYSA-N

CAS Registry83314-01-6

Clinical Trials associated with Bryostatin 1

NCT06190912

/ TerminatedPhase 1IIT

A Single-Arm, Single-Site, Single-Dose Phase 1 Study Assessing the Safety of Bryostatin in the Treatment of Patients With Multiple Sclerosis

This is a single-site, single-arm, single-dose, Phase 1 study of the safety of bryostatin in participants with multiple sclerosis (MS) receiving any disease modifying therapy (DMT).

Start Date26 Jun 2024

Sponsor / Collaborator

The Cleveland Clinic Foundation

[+1]

NCT04538066

/ CompletedPhase 2

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Assessing Safety, Tolerability and Long-term Efficacy of Bryostatin in the Treatment of Moderately Severe Alzheimer's Disease Subjects Not Receiving Memantine Treatment

To evaluate the safety, tolerability, and long-term efficacy of bryostatin 1 (hereafter referred to as bryostatin) for the treatment of moderately severe Alzheimer's disease (AD).

Start Date30 Aug 2020

Sponsor / Collaborator

TAO Synergies, Inc.

[+2]

NCT03560245

/ CompletedPhase 2

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Assessing the Safety, Tolerability and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease Subjects Not Receiving Memantine Treatment

This is a randomized double-blind Placebo-controlled, Phase 2 study comparing bryostatin to placebo for the treatment of moderately severe to severe Alzheimer's disease in subjects not receiving memantine treatment. The study is 15 weeks in duration, including a safety and efficacy evaluation 30 days after the last dose of study drug. Subjects will receive 7 doses of study drug during the study. The primary efficacy endpoint is defined as the change from baseline to Week 13 in the Severe Impairment Battery (SIB) total score.

Start Date20 Jun 2018

Sponsor / Collaborator

TAO Synergies, Inc.

[+1]

100 Clinical Results associated with Bryostatin 1

100 Translational Medicine associated with Bryostatin 1

100 Patents (Medical) associated with Bryostatin 1

621

Literatures (Medical) associated with Bryostatin 1

08 Dec 2025·JCI Insight

Regulation of selective class switching provides long-term therapeutic benefits for hay fever

Article

Author: Nagatake, Takahiro ; Kojima, Hirotatsu ; Sugai, Manabu ; Inomata, Takenori ; Huang, Tianxiang ; Gao, Peng ; Shinkura, Reiko ; Morita, Naoki ; Nakayama, Keiichi I ; Adachi, Takahiro ; Tamano, Ryutaro ; Yamada, Yasuhiro ; Yamamoto, Kohta

IgA protects the body from invaders in the mucosal sites, but its role in allergic diseases, such as hay fever, is poorly understood. We demonstrate an increased susceptibility to cedar-pollen-induced hay fever associated with increasing pollen penetration into the body in IgA-deficient mice, indicating that IgA prevents pollen invasion in the mucosa. We identified bryostatin 1, an anticarcinogenic protein kinase Cδ (PKCδ) activator, as an IgA/IgE class-switching regulator in B cells. Bryostatin 1 enhanced IgA production through induction of germline transcript α (GLTα) via the PKCδ/MEK/ERK/RUNX1 pathway and suppressed IgE by reducing GLTε through the PKCδ/STAT5/ID2 pathway. Production of Th2 cytokines and eosinophil infiltration in the lungs was also reduced. Furthermore, hay fever alleviation by bryostatin 1 demonstrated diminished symptoms in mice in vivo 3 months subsequent to intranasal administration.

01 Dec 2025·Journal for ImmunoTherapy of Cancer

Affinity-matured CD72-targeting nanobody CAR T cells enhance elimination of antigen-low B-cell malignancies

Article

Author: Serrano, Juan Antonio Camara ; Wiita, Arun P ; Phojanakong, Paul ; Carpenter, Christopher ; Shah, Nirali N ; Maus, Marcela V ; Larson, Rebecca C ; Wang, Hao-Wei ; Steri, Veronica ; Ramos, Emilio ; Sahu, Srabani ; Zakraoui, Ons ; Tariq, Isa ; Verma, Amit ; Nix, Matthew A ; Johnson, Haley ; Gil-Alós, Daniel ; Martinez-Lopez, Joaquin ; Izgutdina, Adila ; Parekh, Samir ; Naik, Akul ; Kang, Amrik S ; Yuan, Constance M ; Chen, Szu-Ying ; Salangsang, Fernando ; Patiño-Escobar, Bonell ; Rashid, Tasfia ; Valeri, Antonio ; Temple, William C ; Walunj, Sujata ; Li, Mingcheng ; Aminov, Sarah ; Geng, Huimin ; Takamatsu, Hiroyuki

Background:

Chimeric antigen receptor (CAR) T-cell therapies are highly efficacious for several different hematologic cancers. However, for most CAR T targets it is observed that low surface antigen density on tumors can significantly reduce therapeutic efficacy. In this study, we explore this dynamic in the context of CD72, a surface antigen we recently found as a promising target for refractory B-cell cancers, but for which CD72 low antigen density can lead to therapeutic resistance in preclinical models.

Methods:

Primary samples were accessed via institutional review board-approved protocols. Affinity-matured and humanized nanobody clones were previously described in Temple et al. (2023). CAR T cells were generated via lentiviral transduction. In vitro cytotoxicity assays were performed using luciferase-labeled cell lines. In vivo studies were performed using cell line-derived or patient-derived xenografts implanted in NOD scid gamma mice.

Results:

We first confirmed ubiquitous CD72 expression across a range of primary B-cell non-Hodgkin lymphomas. We further found that after resistance to CD19-directed therapies, across both B-cell acute lymphoblastic leukemia (B-ALL) models and primary tumor samples, surface CD72 expression was largely preserved while CD22 expression was significantly diminished. Affinity maturation of a nanobody targeting CD72, when incorporated into CAR T cells, led to more effective elimination in vitro of isogenic models of CD72 low-expressing tumors. These results suggested that nanobody-based CAR T cells (nanoCARs) may exhibit a similar relationship between binder affinity, antigen expression, and efficacy as previously demonstrated only for single chain variable fragment-based CAR T cells. Surprisingly, however, this significantly improved in vitro efficacy only translated to modest in vivo survival benefit. As a parallel strategy to enhance CAR T function, we found that the small molecule bryostatin could also significantly increase CD72 surface antigen density on B-cell malignancy models. Structural modeling and biochemical analysis identified critical residues improving CD72 antigen recognition of our lead affinity-matured nanobody.

Conclusions:

Together, these findings support affinity-matured CD72 nanoCARs as a potential immunotherapy product for CD19-refractory B-cell cancers. Our results also suggest that for B-ALL in particular, CD72 may be a preferable second-line immunotherapy target over CD22.

28 Nov 2025·JOURNAL OF NATURAL PRODUCTS

Targeting the PKC-Gli Axis: Bryostatin 1 as a Hedgehog Pathway Inhibitor

Article

Author: Billingsley, Kelvin L. ; Tran, UyenPhuong

Aberrant Hedgehog (Hh) signaling contributes to multiple cancers, yet current Smoothened (Smo)-targeted therapies are limited by resistance and relapse. This study investigates bryostatin 1, a clinically relevant natural product from Bugula neritina, for its ability to inhibit Hh signaling downstream of Smo. Bryostatin 1 robustly suppresses Gli transcriptional activity and significantly reduces the expression of key Hh pathway components in a time- and dose-dependent manner. Additionally, it selectively impairs viability in Hh-driven cancer cells while sparing healthy fibroblasts. These compelling results highlight bryostatin 1 as a promising therapeutic candidate for overcoming resistance in aggressive Hh-driven diseases.

News (Medical) associated with Bryostatin 1

26 May 2026

·www.biospace.com

Aphios Corporation Announces Notice of Allowance for Novel Bryoid Composition Patent Targeting Alzheimer’s Disease, Multiple Sclerosis, HIV Latency and Cancer

NORTH READING, Mass.--(BUSINESS WIRE)-- #Alzheimers -- Aphios Corporation today announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for a divisional patent application titled “Bryoid Compositions, Methods of Making and Use Thereof” covering novel Bryoid compounds with potential therapeutic applications in neurodegenerative diseases, HIV latency, cancer, and other amyloid-mediated disorders. The allowed claims relate to a novel Bryoid composition designated B14B, including methods of isolation, purification, and manufacture. The USPTO determined that the claimed Bryoid composition demonstrated novelty and non-obviousness over prior bryostatin-related art. The patent application is part of Aphios’ expanding Bryoid intellectual property portfolio derived from marine bryozoan natural products and advanced purification technologies. The invention was developed with support from the National Institute on Aging and the National Institutes of Health (NIH). Bryoids are structurally related to bryostatins, a class of complex macrocyclic compounds known to modulate protein kinase C (PKC) pathways involved in neurodegeneration, viral latency, and oncology. According to the patent specification, several novel Bryoid compositions demonstrated biological activity comparable to or greater than Bryostatin-1 in stimulating alpha-secretase activity and PKC signaling pathways associated with Alzheimer’s disease and other CNS disorders. The application describes multiple proprietary Bryoid analogs with molecular weights distinct from known Bryostatins 1–20. Experimental data presented in the application demonstrated enhanced alpha-secretase activity and PKC modulation in SHSY-5Y neuroblastoma cells. “Our Bryoid platform represents a significant advancement in the discovery and development of novel marine-derived therapeutics,” said Dr. Trevor P. Castor, Founder and CEO of Aphios Corporation. “This Notice of Allowance further validates the novelty of our Bryoid technology and strengthens our intellectual property estate in neurodegenerative disease therapeutics, HIV latency reversal strategies, and oncology applications.” Aphios’ Bryoid platform combines proprietary extraction, purification, and characterization technologies, including its SuperFluids™ processing platform, to isolate highly pure Bryoid compounds from Bugula neritina and related marine sources. The company believes these compounds may serve as next-generation therapeutics for Alzheimer’s disease, Multiple sclerosis, Parkinson’s disease, HIV-1 latency reversal, and other serious disorders with significant unmet medical need. The Notice of Allowance follows Aphios’ previously issued patents covering Bryoid compositions and expands the company’s growing portfolio of more than 85 issued and pending U.S. and international patents. About Aphios Corporation Aphios Corporation is an emerging growth biotechnology company developing enhanced therapeutics and enabling technologies for drug discovery, drug delivery, and pathogen safety. The company’s proprietary platforms include SuperFluids™ extraction and purification, nanotechnology-based drug delivery systems, and novel therapeutics targeting cancer, infectious diseases, and CNS disorders including Alzheimer’s disease, addiction, pain, and anxiety. This research was in part funded by an SBIR Grant from the National Institute on Aging (NIA), NIH. The content of this release is solely the responsibility of the authors and does not represent the official views of NIA and NIH. For more information, visit . Forward-Looking Statements This press release contains forward-looking statements regarding future events and the future performance of Aphios Corporation, including statements related to the therapeutic potential, development, commercialization, and intellectual property protection of Bryoid compounds and related technologies. Actual results may differ materially from those expressed or implied by these forward-looking statements due to various risks and uncertainties, including scientific, regulatory, clinical, financial, and business factors. Aphios undertakes no obligation to update any forward-looking statements except as required by law. Contacts Dr. Trevor P. Castor Founder & CEO Aphios Corporation (781) 858-7520 tcastor@aphios.com

30 Mar 2021

·www.biospace.com

Aphios Granted US Patent for Novel, More Potent Bryoid to Treat Alzheimer’s diseases, HIV-1 Latency, Prostate Cancer, Glaucoma and Multiple Sclerosis

March 30, 2021 12:00 UTC WOBURN, Mass.--(BUSINESS WIRE)--Aphios Corporation announced today that it has been granted United States Patent No. 10,954,248 entitled “Bryoid Compositions, Methods of Making and Use Thereof.” This patent is part of a family of Aphios patents in Europe (Patent No. 2,925,315, Jan. 16, 2019), Japan (Patent No. 6,440,628, Nov. 30, 2018), Hong Kong (Patent No. HK1,216,891, Nov. 22, 2019), and China (Patent No. ZL201380069328.2, Oct. 19, 2018). Bryoids are a family of Bryostatins, such as Bryostatin-1, that are complex cyclic macrolide molecules. Bryoids were originally isolated from the marine bryozoan, Bugula neritina. Twenty-one Bryoid compositions, known as Bryostatins and are numbered 1-21, not including the present novel Bryostatin, have been identified. According to Dr. Trevor P. Castor, President and CEO, Aphios Corporation, and inventor of this patent: “This Bryoid, Bryostatin-22 is a highly potent nanomolar activator of α-secretase activity in neuroblastoma cell models, being more effective than Bryostatin-1 in increasing activity of all PKC isoforms, particularly the novel PKC isoforms, delta and epsilon.” Aphios is developing Bryoids as therapeutics for neurodegenerative diseases such as Alzheimer’s disease, Multiple Sclerosis, prostate cancer, glaucoma and HIV-1 latency. Bryoids increase the production of a neuronal enzyme, alpha-secretase (α-secretase), which cleaves the amyloid precursor protein into a soluble form inhibiting the formation of toxic, insoluble beta amyloid (Aβ) plaques that are associated with Alzheimer’s disease. In prostate cancer cells, Bryoids inhibit phorbol ester-induced apoptosis by differentially modulating protein kinase C delta (PKC-δ) translocation and preventing PKC-δ-mediated release of tumor necrosis factor-alpha (TNFα). In HIV-1 latency, Bryoids activate cellular transcription factors such as NF-κB (nuclear factor kappa of activated B-cells) that binds the HIV-1 promoter and regulates its transcriptional activity. About Aphios Corporation: Aphios Corporation ( ) is a clinical stage biotechnology company developing enabling technology platforms for improving drug discovery, manufacturing, delivery and safety, and enhanced therapeutics for the treatment of cancers and supportive care, infectious diseases such as HIV, and CNS disorders such as Alzheimer’s disease.

Collaborate

28 May 2020

·www.biospace.com

Neurotrope and NIH Launch Long-Term Trial of Bryostatin in Alzheimer’s

The Phase II study will be performed in collaboration with the National Institutes of Health under a $2.7 million grant. New York-based Neurotrope announced a new long-term trial of Bryostatin-1 for Alzheimer’s disease (AD). The Phase II study will be performed in collaboration with the National Institutes of Health (NIH) under a $2.7 million grant. In September 2019, Neurotrope announced the confirmatory Phase II trial of Bryostatin-1 in moderate to severe AD, saying it did not achieve statistical significance on the primary endpoint. The primary endpoint was change from baseline to Week 13 in the Severe Impairment Battery (SIB) total score. On May 18, 2020, Neurotrope and Metuchen Pharmaceuticals announced a deal where the two companies will merge in an all-stock deal that will become Petros Pharmaceuticals. The expectation is that Petros will become a Nasdaq traded company focused on men’s health. The cornerstone product will be Metuchen’s Stendra (avanafil) for erectile dysfunction. The pipeline will include Metuchen’s in-licensed product H-100 for Peyronie’s disease. Once the deal is closed, Neurotrope’s Bryostatin-1 and all of its existing assets will be spun out into a new, separately traded company, NBI. Neurotrope will retain about $14 million, including the $2.7 million NIH grant. Along with the Phase II trial, Neurotrope plans to continue investigation the drug for Multiple Sclerosis and Fragile X syndrome. “The initiation of a new Bryostatin-1 study in AD, and our efforts in advancing a merger with Metuchen, underscore what we believe is a unique opportunity for our investors to participate in two distinct, publicly-listed companies with potentially meaningful value propositions: Petros Pharmaceuticals, Inc. and the spin-out company NBI,” said Charles S. Ryan, Neurotrope’s chief executive officer. The new Phase II trial is expected to enroll 100 patients. It will evaluate Brystatin-1 in the absence of Namenda for six months, which will include two 11-week dosing cycles. The study will concentrate on AD patients with pre-specified moderately severe and moderate disease, including a group that showed the most benefit in the previous study. It will plan to assess sustained cognitive benefit as measured by the Severe Impairment Battery (SIB) score. Namenda (nemantine) is used to treat moderate to severe dementia related to AD. It is marketed by Allergan. Analysis of the study data will be performed in consultation with Richard Thompson, senior scientist from the Bloomberg School of Public Health at Johns Hopkins University. “We are hopeful that this trial can substantiate certain compelling data with Bryostatin from previous trials, which suggests patients could potentially see improvement in their disease which, I believe, would be transformative as an AD treatment,” said George Perry, professor of Biology and Chemistry, Semmes Distinguished University Chair in Neurobiology, University of Texas at San Antonio and editor-in-chief of the Journal of Alzheimer’s Disease . “When I see this in the context of currently available drugs, I believe Bryostatin could chart a new path in how we treat Alzheimer’s disease.” In the previously mentioned study, Brystostatin-1 (20 mcg) was well tolerated and showed early signals of cognitive improvement, including a 5.0 improvement in SIB score compared to baseline in the Moderate Stratum cohort in the non-Namenda group. This score was sustained through the entire treatment period and for four weeks after completion of the study. A second pilot study used the same treatment protocol without for Namenda for 11 weeks showed similar SIB improvement compared to baseline for the Moderate Stratum cohort.

Phase 2Clinical Result

100 Deals associated with Bryostatin 1

External Link

KEGG	Wiki	ATC	Drug Bank
-	Bryostatin 1	-	DB11752

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 2	United States	TAO Synergies, Inc.	01 Nov 2015
Acinar Cell Carcinoma	Phase 2	United States	National Cancer Institute	01 Mar 2002
Pancreatic Ductal Adenocarcinoma	Phase 2	United States	National Cancer Institute	01 Mar 2002
Advanced Renal Cell Carcinoma	Phase 2	United States	National Cancer Institute	01 Jan 2002
Fallopian Tube Carcinoma	Phase 2	United States	National Cancer Institute	01 Oct 2000
Metastatic Gastric Carcinoma	Phase 2	United States	National Cancer Institute	01 Oct 2000
Ovarian Epithelial Carcinoma	Phase 2	United States	National Cancer Institute	01 Oct 2000
Recurrent ovarian cancer	Phase 2	United States	National Cancer Institute	01 Oct 2000
Recurrent Primary Peritoneal Carcinoma	Phase 2	United States	National Cancer Institute	01 Oct 2000
Metastatic Renal Cell Carcinoma	Phase 2	United States	National Cancer Institute	01 Jun 1999

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06190912 (CTgov)	Phase 1	Multiple Sclerosis	4	Bryostatin 1	onmhtubrtg = gwjxnygzcn deccxrptzw (jukdeujlrq, vybfkurccp - dhydqrhtkp) View more	-	31 Mar 2026
NCT04538066 (CTgov)	Phase 2	Alzheimer Disease	122	Bryostatin 1 (Bryostatin 1)	mizjsiksfo = niyikawdky vhovqcfwyb (cighwqxazy, jknzeisnye - iqjfysxzzx) View more	-	31 Jul 2024
				Placebo (Placebo)	mizjsiksfo = iczswxnhte vhovqcfwyb (cighwqxazy, mthpnxakpz - pxddbqtrua) View more
NCT04538066 (Literature) Manual	Phase 2	Alzheimer Disease	122	Bryostatin 1	rghhuhjhne(shozqdqdmz) = erzgkjonbr rxumbmpkvd (upzanhfcxr, 1.56) View more	Positive	19 Sep 2023
				Placebo	rghhuhjhne(shozqdqdmz) = ssuhlvecvl rxumbmpkvd (upzanhfcxr, 1.51) View more
NCT03560245 (CTgov)	Phase 2	Alzheimer Disease	108	Bryostatin (Bryostatin 20µg)	aalqhasqnv = klkctttcup odpjazutcp (pgbjflrxvg, tthjqdbovr - duixrggojy) View more	-	01 Oct 2020
				Placebo (Placebo)	aalqhasqnv = eokhfhvsfm odpjazutcp (pgbjflrxvg, jcqpneujff - pnrapcicju) View more
NCT02431468 (CTgov)	Phase 2	Alzheimer Disease	147	Bryostatin 1 (Bryostatin 1 20ug)	rrsnbsopzo = xxdoztzeyo jgpstshqxn (ixyatrrlwq, rtzepwdtyv - ufhuzjitvh) View more	-	06 Jul 2018
				Bryostatin 1 (Bryostatin 1 40ug)	rrsnbsopzo = gltwvbtkgz jgpstshqxn (ixyatrrlwq, ukqbxujimb - hmmcbbxfeb) View more
NCT02221947 (CTgov)	Phase 1/2	Alzheimer Disease	9	Bryostatin 1 (Bryostatin 1)	lhthmeoqog = mqpngjaiqk qglihavotq (ilkybaubdv, yuttoiwila - hukthoikok) View more	-	21 Apr 2016
				Placebo (Placebo)	lhthmeoqog = wntgfxkdbf qglihavotq (ilkybaubdv, xsahpretsw - aocyyqlldo) View more
NCT00031694 (CTgov)	Phase 2	Acinar Cell Carcinoma \| Pancreatic Ductal Adenocarcinoma	19	bryostatin 1+paclitaxel	rmhcixnwvf = xqiuloefiw nvkvvvejfy (boofafkbyn, ogchbtzmxv - rvroighyml) View more	-	21 Apr 2015
NCT00006389 (CTgov)	Phase 2	Metastatic Gastric Carcinoma	12	laboratory biomarker analysis+bryostatin 1+cisplatin	tzveghotkn = msculasncy qginlvqalj (wfcvpyfcko, pisuoxenbf - mrqpfrbgyo) View more	-	01 Oct 2014
NCT00004144 (Pubmed \| Clin Cancer Res)	Phase 1	Solid tumor \| Advanced cancer	36	Bryostatin 1	vtgmcnmqfh(gmlylwjgfi) = sgisuelcqe rhjuwlcyxo (sgocuqayku ) View more	-	01 Dec 2006
				Gemcitabine	vtgmcnmqfh(gmlylwjgfi) = krwfxarzml rhjuwlcyxo (sgocuqayku )
ASCO2004	Phase 2	Renal Cell Carcinoma	33	Interleukin-2	kzjelqzhav(lrwtzdrror) = vnssjouobi arcaaurcbf (akelmmmsbx, 377–577) View more	Negative	15 Jul 2004

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