NPASS Compound

Natural Product: NPC603923

Natural Product ID	NPC603923
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QJOJMIGBIPHDPW-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL558681
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 25 26 0 0 0 0 0 0 0 0999 V2000 1.2370 -1.7015 1.0274 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7941 -0.5907 0.4149 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0185 -0.1056 0.8957 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8221 -1.0161 2.3547 Br 0 0 0 0 0 0 0 0 0 0 0 0 3.6411 0.9804 0.3594 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9971 1.5976 -0.7052 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7903 3.1315 -1.5279 Br 0 0 0 0 0 0 0 0 0 0 0 0 1.8002 1.1401 -1.1910 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1612 0.0141 -0.6303 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0400 -0.3570 -1.1983 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2553 -0.4640 -0.5628 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8710 0.7566 -0.2432 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2612 1.9686 -0.5625 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0871 0.6903 0.3907 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9327 2.3644 0.8296 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.6998 -0.5106 0.7114 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0998 -1.7129 0.3991 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9139 -3.3836 0.8253 Br 0 0 0 0 0 0 0 0 0 0 0 0 -1.8740 -1.6536 -0.2408 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0573 -3.3255 -0.7428 Br 0 0 0 0 0 0 0 0 0 0 0 0 1.7729 -2.5781 1.0095 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5758 1.3457 0.7311 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3384 1.6524 -2.0192 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1872 2.2785 -1.5424 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6694 -0.5209 1.2176 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 3 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 9 2 1 0 19 11 1 0 1 21 1 0 5 22 1 0 8 23 1 0 13 24 1 0 16 25 1 0 M END

Standard InCHIKey	QJOJMIGBIPHDPW-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H5Br5O3/c13-4-1-6(15)10(18)8(2-4)20-12-9(17)5(14)3-7(16)11(12)19/h1-3,18-19H
SMILES	Oc1c(Br)cc(Br)cc1Oc1c(O)c(Br)cc(Br)c1Br

Calculated Properties

Physi-Chem Properties

Molecular Weight:	591.62	Volume:	305.965 ? Van der Waals volume.
Dense:	1.934	LogP:	5.013 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.112 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.437 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	12.0
TPSA:	49.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.38	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.874	Fsp³:	0.0
MCE-18:	15.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.919	Fluc inhibitor:	0.319 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.026 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.319 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.998	Promiscuous compounds:	0.438

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.042	MDCK Permeability:	-4.652
Pgp-inhibitor:	0.301	Pgp-substrate:	0.0
PAMPA:	0.674 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.277
20% Bioavailability (F20%):	0.011	30% Bioavailability (F30%):	0.132
50% Bioavailability (F50%):	0.019

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.058	MRP1:	0.984
Plasma Protein Binding (PPB):	97.146%	Volume Distribution (VD):	-0.116
Fu:	1.179% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.941
OATP1B3 inhibitor:	0.958	BCRP inhibitor:	0.118
BSEP inhibitor:	0.992

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.015
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.042
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.046 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

4.95

Half-life (T1/2):

2.123

ADMET: Toxicity

hERG Blockers:	0.106	hERG Blockers (10um):	0.682
Human Hepatotoxicity (H-HT):	0.224	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.137	Rat Oral Acute Toxicity:	0.924
Maximum Recommended Daily Dose:	0.993	Skin Sensitization:	0.993
Carcinogencity:	0.797	Eye Corrosion:	0.994
Eye Irritation:	0.999	Respiratory Toxicity:	0.466
Drug-induced Neurotoxicity:	0.664	Ototoxicity:	0.051
Hematotoxicity:	0.006	Drug-induced Nephrotoxicity:	0.077
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.068
A549 Cytotoxicity:	0.591	Hek293 Cytotoxicity:	0.424
BCF:	1.767 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	5.644 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.168 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.995 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO4485	Lamellodysidea herbacea	Species	Dysideidae	Eukaryota	n.a.	Indonesian	n.a.	PMID[17311456]
NPO4485	Lamellodysidea herbacea	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[28841316]
NPO4485	Lamellodysidea herbacea	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4485	Lamellodysidea herbacea	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	2
MIC	7
MNTD	1

Activity Type	# Activity
Individual protein	1
Organism	7
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT57	Individual protein	Induced myeloid leukemia cell differentiation protein Mcl-1	Homo sapiens	IC50	>	10.0	ug.mL-1	PMID[19323567]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	50.0	ug.mL-1	PMID[27399938]
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	50.0	ug.mL-1	PMID[27399938]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	MNTD	=	50.0	ug ml-1	PMID[27399938]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	100.0	ug.mL-1	PMID[27399938]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	0.31	ug.mL-1	PMID[27399938]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	1.6	ug.mL-1	PMID[27399938]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	>	50.0	ug.mL-1	PMID[27399938]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	MIC	=	3.1	ug.mL-1	PMID[27399938]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC603923 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	41403
0.1-0.2	8336
0.2-0.3	74
0.3-0.4	29
0.4-0.5	1
0.5-0.6	8
0.6-0.7	5
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7073	Intermediate Similarity	NPC64130
0.7	Intermediate Similarity	NPC137922
0.6923	Remote Similarity	NPC196371
0.6667	Remote Similarity	NPC63317
0.6585	Remote Similarity	NPC40302
0.6341	Remote Similarity	NPC104124
0.6098	Remote Similarity	NPC601831
0.587	Remote Similarity	NPC230013
0.587	Remote Similarity	NPC483502
0.587	Remote Similarity	NPC81149
0.5814	Remote Similarity	NPC97157
0.5581	Remote Similarity	NPC44270
0.5532	Remote Similarity	NPC88733
0.5435	Remote Similarity	NPC68350
0.5217	Remote Similarity	NPC170824

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC603923 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7176
0.1-0.2	1947
0.2-0.3	25
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7059	Intermediate Similarity	NPD911	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data