Fig. 1 · Structure

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Bryostatin 1

Cat. No. A10261 CAS 83314-01-6

PKC inhibitor

Bryostatin 1 is a macrolactone isolated from the marine bryozoan, Bugula neritina, that modulates protein kinase C (PKC) activity. Bryostain 1 induces an initial rapid activation and autophosphorylation of PKC that results in the translocation of the PKC enzyme to the membrane.

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Biological Activity

Bioactivity / Mechanism

Bryostatin 1 changes PKC protein abundance in a concentration- and isoform-dependent manner. In U937 cells, 24-hour treatment down-regulated PKCβII and PKCδ; the PKCδ response was biphasic, with less down-regulation at higher concentrations. The reported EC50 values describe protein down-regulation rather than acute inhibition of kinase activity. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
HIV-1  

In Vitro Studies

In U937 leukemia cells, bryostatin 1 produced limited, biphasic growth inhibition and much less cell attachment than PMA after 60 hours. A separate co-treatment arm showed that bryostatin 1 opposed PMA-induced growth inhibition and attachment. These results illustrate that its cellular effects differ from those of PMA under the tested conditions. [1]

Limited U937 growth inhibition and attachment, with antagonism of PMA

Cell-based study · Human U937 monocytic leukemia cells [1]

Over 60 h, bryostatin 1 caused much less growth inhibition and cell attachment than PMA. Its small response was biphasic. Co-treatment with bryostatin 1 opposed PMA-induced growth inhibition and attachment. Five independent experiments support the plotted growth and attachment data; results are specific to this cell model and schedule.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Total attached plus floating cells, relative to vehicle controlCell number relative to DMSO Limited, biphasic growth inhibition with bryostatin 1 alone; suppression of PMA-induced growth inhibition with co-treatment[1]
Attached cells as a percentage of total cellsAttachment Much less attachment with bryostatin 1 than PMA; co-treatment opposed PMA-induced attachment[1]

Literature-Reported Treatment Conditions

Treatment concentration
Bryostatin 1: 0.1–1000 nM concentration series; PMA comparator: 0.1–1000 nM.
Exposure duration
60 h
Method
Treatment 24 h after plating; count attached and floating cells.
Vehicle
0.1% DMSO in each sample
Co-treatment
Separate co-treatment arm: 10 nM PMA + 1000 nM bryostatin 1. Single-agent effects are reported separately.
Reported limits
No fitted growth-inhibition IC50 reported for the selected bryostatin 1 response. No Adooq lot tested.
Methods and source locations

Compound reported in the paper: Bryostatin 1; Compound label in the paper: bryostatin 1

Reported bryostatin 1 experiments; supplier and lot equivalence to Adooq A10261 were not established. No salt conversion or stereoisomer substitution is made.

Figure 2A–B and caption; Results: Biological Responses in U937 Leukemia Cells (text mis-cites Figure 1A–B); Materials; The growth and attachment of U937 cells

Total attached plus floating cells, relative to vehicle control: Beckman particle/Coulter counting after 60 h; plotted mean ± SEM, five independent experiments. No exact percentage inferred from bars. — Figure 2A and caption; The growth and attachment of U937 cells

Attached cells as a percentage of total cells: Attached cells counted after trypsinization and combined with floating-cell counts; 60 h treatment; plotted mean ± SEM, five independent experiments. — Figure 2B and caption; The growth and attachment of U937 cells

Concentration-dependent PKC protein down-regulation in U937 cells

Cell-based study · Human U937 monocytic leukemia cells; total-cell PKCβII and PKCδ protein [1]

After 24 h, bryostatin 1 reduced PKCβII and PKCδ protein abundance. PKCδ showed a biphasic concentration-response with less down-regulation at higher concentrations. PMA caused less PKCβII down-regulation and little PKCδ down-regulation. These endpoints quantify protein abundance, not acute kinase inhibition.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Down-regulation of PKCβII protein after 24 hEC50 0.310 ± 0.005 nM[1]
Down-regulation of PKCδ protein after 24 hEC50 0.083 ± 0.008 nM[1]
High-concentration behavior of PKCδ protein abundanceConcentration-response shape Biphasic down-regulation: PKCδ signal rises again at higher bryostatin 1 concentrations[1]

Literature-Reported Treatment Conditions

Treatment concentration
Varied bryostatin 1 concentrations as shown in Figure 3; PMA and bryostatin 7 compared in parallel.
Exposure duration
24 h
Method
Simple Western capillary immunoassay of total cell lysates, normalized to loading controls and DMSO-treated cells; representative conventional immunoblots shown.
Vehicle
DMSO-treated cells were the reference control; final DMSO percentage is not specified in the Simple Western subsection.
Reported limits
These are protein down-regulation EC50 values, not catalytic IC50, binding affinity or treatment recommendations. The fitted-EC50 uncertainty type is not explicitly identified.
Methods and source locations

Compound reported in the paper: Bryostatin 1; Compound label in the paper: bryostatin 1

Reported bryostatin 1 experiments; supplier and lot equivalence to Adooq A10261 were not established. No salt conversion or stereoisomer substitution is made.

Figure 3A–B and caption; Results: Down regulation of PKC isoforms in U937 cells; Materials; Simple Western

Down-regulation of PKCβII protein after 24 h: Author-reported down-regulation EC50; Simple Western signal normalized to β-actin or α-tubulin and DMSO control. Figure 3 data are mean ± SEM from three independent experiments; the uncertainty type of the fitted EC50 is not separately specified. — Results: Down regulation of PKC isoforms in U937 cells; Figure 3A and caption; Simple Western

Down-regulation of PKCδ protein after 24 h: Author-reported EC50 for the down-regulating component of a biphasic response. Simple Western normalization as described for Figure 3. The ± on the fitted EC50 is retained without assigning an unreported uncertainty type. — Results: Down regulation of PKC isoforms in U937 cells; Figure 3B and caption; Simple Western

High-concentration behavior of PKCδ protein abundance: Figure 3B viewed with representative blots and quantified curves. Plotted data: mean ± SEM, three independent experiments; no exact high-concentration percentage inferred. — Figure 3B and caption; Results: Down regulation of PKC isoforms in U937 cells

In Vivo Studies

In a rat global ischemia/hypoxia model, postischemic bryostatin-1 treatment preserved retention of a previously learned spatial task. Treated ischemic rats retained target preference two weeks after the final dose, whereas untreated ischemic rats did not; sham and drug-only controls also retained preference. Visible-platform testing found no significant group difference. This preclinical result does not establish clinical efficacy. [2]

Retention of previously learned spatial memory after global ischemia/hypoxia

Animal study · Adult male Wistar rats (225–250 g); four randomized groups, eight rats/group; spatial task learned before ischemia/hypoxia [2]

In the separate pretraining/retention paradigm, all four groups learned the water-maze task before assignment. Bryostatin-1 began 24 h after ischemia/hypoxia and continued for 5 weeks. Two weeks after the last dose, the treated ischemic rats retained target preference, while untreated ischemic rats did not. Sham and drug-only controls also retained preference. Visible-platform testing found no significant group difference. This is a rat global-ischemia/hypoxia result; PKC causation and clinical efficacy were not established by this experiment.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Target quadrant distance divided by mean nontarget quadrant distance in the second probe testANOVA target quadrant ratio Overall groups: F3,31 = 3.222, P < 0.05; ischemia versus ischemia + bryostatin-1: F1,15 = 7.297, P < 0.05[2]
Sensorimotor ability and escape motivation after the retention probeVisible-platform group comparison F3,31 = 0.218, P > 0.05[2]
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Sham-operated controlFour parallel groups: sham-operated control, ischemia/hypoxia, ischemia/hypoxia + bryostatin-1, bryostatin-1 only.Target preference retained in the second probe test; no significant difference from the ischemia + bryostatin-1 group in target quadrant ratio.[2]
Ischemia/hypoxiaFour parallel groups: sham-operated control, ischemia/hypoxia, ischemia/hypoxia + bryostatin-1, bryostatin-1 only.Lost target preference in the second probe test (P > 0.05); longer latency to the prior platform location.[2]
Ischemia/hypoxia + bryostatin-1
15 μg/m²
Four parallel groups: sham-operated control, ischemia/hypoxia, ischemia/hypoxia + bryostatin-1, bryostatin-1 only.Retained target preference (P < 0.005); target quadrant ratio differed from untreated ischemia (P < 0.05).[2]
Bryostatin-1 only
15 μg/m²
Four parallel groups: sham-operated control, ischemia/hypoxia, ischemia/hypoxia + bryostatin-1, bryostatin-1 only.Retained target preference; target quadrant ratio was not significantly different from sham control (P > 0.05).[2]
Sham-operated control
Model: Adult male Wistar rats, 225–250 g; n = 8 per group in Figure 4.
Reported limits: Vehicle and formulation not specified in the read scope. Behavioral blinding is not stated. No conversion of μg/m² to μg/kg is made.
Ischemia/hypoxia
Model: Adult male Wistar rats, 225–250 g; n = 8 per group in Figure 4.
Reported limits: Vehicle and formulation not specified in the read scope. Behavioral blinding is not stated. No conversion of μg/m² to μg/kg is made.
Ischemia/hypoxia + bryostatin-1
Model: Adult male Wistar rats, 225–250 g; n = 8 per group in Figure 4.
Route: Tail-vein intravenous injection
Frequency: Two doses/week
Treatment course: 10 doses over 5 weeks, starting 24 h after the ischemic/hypoxic episode (or corresponding drug-only group).
Reported limits: Vehicle and formulation not specified in the read scope. Behavioral blinding is not stated. No conversion of μg/m² to μg/kg is made.
Bryostatin-1 only
Model: Adult male Wistar rats, 225–250 g; n = 8 per group in Figure 4.
Route: Tail-vein intravenous injection
Frequency: Two doses/week
Treatment course: 10 doses over 5 weeks, starting 24 h after the ischemic/hypoxic episode (or corresponding drug-only group).
Reported limits: Vehicle and formulation not specified in the read scope. Behavioral blinding is not stated. No conversion of μg/m² to μg/kg is made.
Methods and source locations

Compound reported in the paper: Bryostatin 1; Compound label in the paper: bryostatin-1

Reported bryostatin 1 experiments; supplier and lot equivalence to Adooq A10261 were not established. No salt conversion or stereoisomer substitution is made.

Results: Bryostatin-1 Rescues Learned Spatial Experiences from Global Cerebral Ischemic Impairment; Figure 4A–G and caption; Materials and Methods: Animals, Cerebral Ischemia/Hypoxia, and Drug Treatments; Spatial Learning and Memory; Visible Platform Test; statistics

Target quadrant distance divided by mean nontarget quadrant distance in the second probe test: Second probe test two weeks after the last dose; Figure 4F, n = 8 rats/group. Figure legend gives means ± SEM. Reported statistical degrees of freedom are retained verbatim, without reconstructing the raw data. — Results: Bryostatin-1 Rescues Learned Spatial Experiences; Figure 4F and caption

Sensorimotor ability and escape motivation after the retention probe: Visible-platform test after the second probe; no significant difference among four groups. No numerical equality or equivalence claim is made. — Results: Bryostatin-1 Rescues Learned Spatial Experiences, final sentence; Materials and Methods: Visible Platform Test

Sham-operated control · Results: Bryostatin-1 Rescues Learned Spatial Experiences from Global Cerebral Ischemic Impairment; Figure 4A–G and caption; Materials and Methods: Animals, Cerebral Ischemia/Hypoxia, and Drug Treatments; Spatial Learning and Memory; Visible Platform Test; statistics

Ischemia/hypoxia · Results: Bryostatin-1 Rescues Learned Spatial Experiences from Global Cerebral Ischemic Impairment; Figure 4A–G and caption; Materials and Methods: Animals, Cerebral Ischemia/Hypoxia, and Drug Treatments; Spatial Learning and Memory; Visible Platform Test; statistics

Ischemia/hypoxia + bryostatin-1 · Results: Bryostatin-1 Rescues Learned Spatial Experiences from Global Cerebral Ischemic Impairment; Figure 4A–G and caption; Materials and Methods: Animals, Cerebral Ischemia/Hypoxia, and Drug Treatments; Spatial Learning and Memory; Visible Platform Test; statistics

Bryostatin-1 only · Results: Bryostatin-1 Rescues Learned Spatial Experiences from Global Cerebral Ischemic Impairment; Figure 4A–G and caption; Materials and Methods: Animals, Cerebral Ischemia/Hypoxia, and Drug Treatments; Spatial Learning and Memory; Visible Platform Test; statistics

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 83314-01-6
Applications PKC inhibitor
Formula C47H68O17
Molecular Weight 905.03
Synonyms NSC 339555
SMILES
CCC/C=C/C=C/C(=O)O[C@H]1/C(=C/C(=O)OC)/C[C@H]2C[C@@H](OC(=O)C[C@@H](C[C@@H]3C[C@@H](C([C@@](O3)(C[C@@H]4C/C(=C/C(=O)OC)/C[C@@H](O4)/C=C/C([C@@]1(O2)O)(C)C)O)(C)C)OC(=O)C)O)[C@@H](C)O

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Noemi Kedei, Nancy E Lewin, Tamas Geczy, et al. The Biological Profile of the Less Lipophilic and Synthetically More Accessible Bryostatin 7 Closely Resembles That of Bryostatin 1 ACS chemical biology (2013). PMID: 23369356 DOI: 10.1021/cb300671s Source material
  2. [2] Miao-Kun Sun, Jarin Hongpaisan, Daniel L Alkon. Postischemic PKC activation rescues retrograde and anterograde long-term memory Proceedings of the National Academy of Sciences of the United States of America (2009). PMID: 19667190 DOI: 10.1073/pnas.0907842106 Source material

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