NPASS Compound

Natural Product: NPC603691

Natural Product ID	NPC603691
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KSHCTKZLHCSARH-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1700548
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 30 31 0 0 0 0 0 0 0 0999 V2000 -0.1482 0.4962 -1.0645 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7481 0.1678 -0.0224 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1239 -0.2415 1.1851 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1204 -0.4278 1.4684 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3299 -0.3165 0.6847 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4407 0.3137 1.2981 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6717 0.3889 0.7203 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8296 -0.1835 -0.5281 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7786 -0.7995 -1.1428 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5232 -0.8761 -0.5479 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5026 -1.5354 -1.2226 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2284 0.2234 -0.0941 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0430 -0.1096 0.9428 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4302 -0.0273 0.7771 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9602 0.3853 -0.4203 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1386 0.7240 -1.4749 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7601 0.6446 -1.3170 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9474 0.9801 -2.3617 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8109 -0.4410 2.0698 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3613 -0.7557 2.5560 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2823 0.7516 2.2753 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5266 0.8802 1.2049 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7873 -0.1486 -1.0294 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8979 -1.2472 -2.1166 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4085 -1.4906 -2.2433 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6456 -0.4327 1.8758 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0254 -0.3027 1.6303 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0240 0.4525 -0.5595 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5140 1.0538 -2.4351 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9125 1.8735 -2.8226 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 3 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 2 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 10 5 1 0 17 12 1 0 3 19 1 0 4 20 1 0 6 21 1 0 7 22 1 0 8 23 1 0 9 24 1 0 11 25 1 0 13 26 1 0 14 27 1 0 15 28 1 0 16 29 1 0 18 30 1 0 M END

Standard InCHIKey	KSHCTKZLHCSARH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H12O3/c16-13-7-3-1-5-11(13)9-10-15(18)12-6-2-4-8-14(12)17/h1-10,16-17H
SMILES	O=C(C=Cc1ccccc1O)c1ccccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	240.08	Volume:	256.162 ? Van der Waals volume.
Dense:	0.937	LogP:	3.419 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.204 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.081 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	14.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.64	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.942	Fsp³:	0.0
MCE-18:	11.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.766	Fluc inhibitor:	0.999 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.55 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.471 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.997	Promiscuous compounds:	0.431

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.873	MDCK Permeability:	-4.758
Pgp-inhibitor:	0.583	Pgp-substrate:	0.063
PAMPA:	0.187 ? 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):	0.019
20% Bioavailability (F20%):	0.194	30% Bioavailability (F30%):	0.723
50% Bioavailability (F50%):	0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.243	MRP1:	0.278
Plasma Protein Binding (PPB):	98.791%	Volume Distribution (VD):	-0.876
Fu:	0.783% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.964
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.327
BSEP inhibitor:	0.674

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.651
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.524	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.832	CYP2D6-substrate:	0.183
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.94
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.69 ? 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):

5.943

Half-life (T1/2):

0.782

ADMET: Toxicity

hERG Blockers:	0.073	hERG Blockers (10um):	0.483
Human Hepatotoxicity (H-HT):	0.465	Drug-induced Liver Injury (DILI):	0.083
AMES Toxicity:	0.5	Rat Oral Acute Toxicity:	0.183
Maximum Recommended Daily Dose:	0.368	Skin Sensitization:	0.923
Carcinogencity:	0.142	Eye Corrosion:	0.124
Eye Irritation:	0.994	Respiratory Toxicity:	0.839
Drug-induced Neurotoxicity:	0.251	Ototoxicity:	0.18
Hematotoxicity:	0.082	Drug-induced Nephrotoxicity:	0.367
Genotoxicity:	0.294	RPMI-8226 Immunitoxicity:	0.122
A549 Cytotoxicity:	0.459	Hek293 Cytotoxicity:	0.484
BCF:	1.344 ? 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:	4.177 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.157 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.798 ? 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
NPO1659	Primula denticulata	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1659	Primula denticulata	Species	Primulaceae	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
Potency	24
AbsAC26_uM	1

Activity Type	# Activity
Individual protein	19
Cell line	1
Unchecked	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	29092.9	nM	PubChem BioAssay data set
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	Potency	n.a.	7943.3	nM	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	14125.4	nM	PubChem BioAssay data set
NPT11	Individual protein	Guanine nucleotide-binding protein G(s), subunit alpha	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT135	Individual protein	Chromobox protein homolog 1	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT159	Individual protein	Aberrant vpr protein	Human immunodeficiency virus 1	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	25118.9	nM	PubChem BioAssay data set
NPT9	Individual protein	DNA polymerase eta	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	14581.0	nM	PubChem BioAssay data set
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	18356.4	nM	PubChem BioAssay data set
NPT831	Individual protein	Serine/threonine-protein kinase PLK1	Homo sapiens	Potency	n.a.	21192.3	nM	PubChem BioAssay data set
NPT888	Individual protein	78 kDa glucose-regulated protein	Homo sapiens	Potency	n.a.	12589.3	nM	PubChem BioAssay data set
NPT920	Individual protein	Alpha-synuclein	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT478	Individual protein	Ataxin-2	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT861	Individual protein	Isocitrate dehydrogenase [NADP] cytoplasmic	Homo sapiens	Potency	n.a.	23109.3	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	25118.9	nM	PubChem BioAssay data set
NPT532	Individual protein	Lysine-specific demethylase 4A	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell line	HepG2	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	18356.4	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	AbsAC26_uM	n.a.	2.85	uM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	25118.9	nM	PubChem BioAssay data set

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 NPC603691 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	25768
0.1-0.2	20530
0.2-0.3	3226
0.3-0.4	266
0.4-0.5	53
0.5-0.6	9
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8056	Intermediate Similarity	NPC224273
0.7714	Intermediate Similarity	NPC141523
0.6486	Remote Similarity	NPC267552
0.6286	Remote Similarity	NPC283711
0.6	Remote Similarity	NPC337373
0.5854	Remote Similarity	NPC297186
0.5745	Remote Similarity	NPC12165
0.5455	Remote Similarity	NPC224584
0.5366	Remote Similarity	NPC19174
0.5366	Remote Similarity	NPC115159
0.5366	Remote Similarity	NPC158222
0.5227	Remote Similarity	NPC13238
0.5116	Remote Similarity	NPC122793
0.5111	Remote Similarity	NPC64359

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC603691 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4244
0.1-0.2	4653
0.2-0.3	246
0.3-0.4	5
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
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
		NPD

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