NPASS Compound

Natural Product: NPC481949

Natural Product ID	NPC481949
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QOFMXRVXOUYNRO-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000023] Naphthalenes [CHEMONTID:0000153] Naphthoquinones

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 26 27 0 0 0 0 0 0 0 0999 V2000 -3.6216 1.6667 -0.1324 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5746 0.6284 0.0299 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8424 -0.6289 0.3550 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7489 -1.5653 0.4889 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0123 -2.7573 0.7979 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3573 -1.1673 0.2767 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0707 0.1525 -0.0650 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2166 0.5860 -0.2770 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2408 -0.3224 -0.1440 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9821 -1.6334 0.1932 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6997 -2.0408 0.3986 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3938 -3.3546 0.7404 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5504 0.0533 -0.3439 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8224 1.3960 -0.6899 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1835 1.0600 -0.1903 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9331 2.2611 -0.5004 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4672 2.1086 -1.1482 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6333 1.2900 0.0200 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3465 2.4998 0.5760 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8842 -0.8758 0.5015 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4107 1.6322 -0.5450 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7768 -2.3648 0.3029 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9827 -3.8629 1.3781 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8960 1.5370 -0.9568 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1750 1.6661 -1.5691 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5287 2.0359 0.1427 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 4 5 2 0 4 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 9 13 1 0 13 14 1 0 7 15 1 0 15 16 2 0 15 2 1 0 11 6 1 0 1 17 1 0 1 18 1 0 1 19 1 0 3 20 1 0 8 21 1 0 10 22 1 0 12 23 1 0 14 24 1 0 14 25 1 0 14 26 1 0 M END

Standard InCHIKey	QOFMXRVXOUYNRO-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H10O4/c1-6-3-9(13)11-8(12(6)15)4-7(16-2)5-10(11)14/h3-5,14H,1-2H3
SMILES	CC1=CC(=O)c2c(cc(cc2O)OC)C1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	218.06	Volume:	218.338 ? Van der Waals volume.
Dense:	0.999	LogP:	2.371 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.517 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.385 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	13.0
TPSA:	63.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.779	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.377	Fsp³:	0.167
MCE-18:	26.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.136	Fluc inhibitor:	0.662 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.653 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.45 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.663	Promiscuous compounds:	0.318

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.852	MDCK Permeability:	-4.677
Pgp-inhibitor:	0.037	Pgp-substrate:	0.006
PAMPA:	0.902 ? 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):	0.403
20% Bioavailability (F20%):	0.027	30% Bioavailability (F30%):	0.199
50% Bioavailability (F50%):	0.472

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.89
Plasma Protein Binding (PPB):	93.937%	Volume Distribution (VD):	0.08
Fu:	5.084% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.989
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.003
BSEP inhibitor:	0.447

ADMET: Metabolism

CYP1A2-inhibitor:	0.997	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.871
CYP2C9-inhibitor:	0.383	CYP2C9-substrate:	0.996
CYP2D6-inhibitor:	0.008	CYP2D6-substrate:	0.74
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.723
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.975
HLM stability:	0.822 ? 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):

7.165

Half-life (T1/2):

0.966

ADMET: Toxicity

hERG Blockers:	0.077	hERG Blockers (10um):	0.488
Human Hepatotoxicity (H-HT):	0.763	Drug-induced Liver Injury (DILI):	0.827
AMES Toxicity:	0.809	Rat Oral Acute Toxicity:	0.604
Maximum Recommended Daily Dose:	0.746	Skin Sensitization:	0.906
Carcinogencity:	0.785	Eye Corrosion:	0.382
Eye Irritation:	0.996	Respiratory Toxicity:	0.927
Drug-induced Neurotoxicity:	0.553	Ototoxicity:	0.279
Hematotoxicity:	0.686	Drug-induced Nephrotoxicity:	0.419
Genotoxicity:	0.798	RPMI-8226 Immunitoxicity:	0.146
A549 Cytotoxicity:	0.306	Hek293 Cytotoxicity:	0.512
BCF:	2.015 ? 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:	4.512 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.639 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.073 ? 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
NPO41066	Teratosphaeria sp. FL2137	Strain	Teratosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29373790]
NPO41066	Teratosphaeria sp. FL2137	Strain	Teratosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	5

Activity Type	# Activity
Cell line	5

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	3100.0	nM	PMID[29373790]
NPT395	Cell line	SF-268	Homo sapiens	IC50	>	5000.0	nM	PMID[29373790]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	>	5000.0	nM	PMID[29373790]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	1200.0	nM	PMID[29373790]
NPT23103	Cell line	PC-3M	Homo sapiens	IC50	=	4900.0	nM	PMID[29373790]

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 NPC481949 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	17435
0.1-0.2	26617
0.2-0.3	5332
0.3-0.4	408
0.4-0.5	42
0.5-0.6	21
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	Natural Product ID
0.5833	Remote Similarity	NPC480618
0.549	Remote Similarity	NPC155686
0.549	Remote Similarity	NPC602483
0.5455	Remote Similarity	NPC285829
0.5455	Remote Similarity	NPC182646
0.5385	Remote Similarity	NPC610271
0.537	Remote Similarity	NPC73341
0.537	Remote Similarity	NPC486435
0.5333	Remote Similarity	NPC486393
0.5283	Remote Similarity	NPC475201
0.5283	Remote Similarity	NPC132990
0.5283	Remote Similarity	NPC603318
0.5273	Remote Similarity	NPC480614
0.5238	Remote Similarity	NPC45537
0.5238	Remote Similarity	NPC486396
0.5238	Remote Similarity	NPC609532
0.5208	Remote Similarity	NPC84273
0.5185	Remote Similarity	NPC46882
0.5185	Remote Similarity	NPC601158
0.5111	Remote Similarity	NPC180685
0.5091	Remote Similarity	NPC480607

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC481949 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4009
0.1-0.2	4949
0.2-0.3	186
0.3-0.4	6
0.4-0.5	0
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