NPASS Compound

Natural Product: NPC300149

Natural Product ID	NPC300149
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VOUJHLROTVTYMT-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	636743
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0002497] Indoles

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 34 37 0 0 0 0 0 0 0 0999 V2000 3.9447 1.7338 -0.5618 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1742 1.1941 -0.2991 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2169 -0.1204 0.1383 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1011 -0.9085 0.3233 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8505 -0.3566 0.0574 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8023 0.9620 -0.3844 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9277 -1.3284 0.2949 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6463 -2.4777 0.7039 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9413 -2.1833 0.7080 N 0 0 0 0 0 0 0 0 0 0 0 0 0.5032 -1.2995 0.2894 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0636 -2.4772 0.4125 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4562 -0.2483 0.1830 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1508 0.9609 0.2359 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9069 -0.5095 -0.0021 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5442 -1.7090 -0.1201 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8677 -1.4388 -0.2824 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.0830 -0.1401 -0.2713 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2605 0.5860 -0.4012 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2188 1.9528 -0.3550 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9914 2.5899 -0.1779 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8304 1.8815 -0.0496 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8541 0.5101 -0.0937 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8635 2.7491 -0.9035 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1059 1.7540 -0.4203 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1890 -0.5894 0.3593 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8749 1.3866 -0.6290 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2634 -3.4536 0.9786 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7366 -2.8181 0.9644 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1296 -2.7067 -0.1000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5814 -2.1866 -0.3965 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2167 0.1099 -0.5386 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1267 2.5137 -0.4551 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9524 3.6668 -0.1407 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9071 2.4005 0.0850 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 2 0 8 9 1 0 7 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 6 1 1 0 22 14 1 0 9 4 1 0 22 17 1 0 1 23 1 0 2 24 1 0 3 25 1 0 6 26 1 0 8 27 1 0 9 28 1 0 15 29 1 0 16 30 1 0 18 31 1 0 19 32 1 0 20 33 1 0 21 34 1 0 M END

Standard InCHIKey	VOUJHLROTVTYMT-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H12N2O2/c21-17(13-9-19-15-7-3-1-5-11(13)15)18(22)14-10-20-16-8-4-2-6-12(14)16/h1-10,19-20H
SMILES	c1ccc2c(c1)c(c[nH]2)C(=O)C(=O)c1c[nH]c2ccccc12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	288.09	Volume:	298.868 ? Van der Waals volume.
Dense:	0.964	LogP:	3.319 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.78 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.628 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	22.0
TPSA:	65.72 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.446	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.119	Fsp³:	0.0
MCE-18:	20.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.891	Fluc inhibitor:	0.947 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.279 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.593 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.368	Promiscuous compounds:	0.975

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.803	MDCK Permeability:	-4.64
Pgp-inhibitor:	0.984	Pgp-substrate:	0.0
PAMPA:	0.244 ? 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):	0.353
20% Bioavailability (F20%):	0.003	30% Bioavailability (F30%):	0.818
50% Bioavailability (F50%):	0.635

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.003
Plasma Protein Binding (PPB):	96.73%	Volume Distribution (VD):	-0.017
Fu:	2.745% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.984
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.443
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.048	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.813
CYP2C9-inhibitor:	0.108	CYP2C9-substrate:	0.993
CYP2D6-inhibitor:	0.915	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	0.024
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.969 ? 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):

6.555

Half-life (T1/2):

0.849

ADMET: Toxicity

hERG Blockers:	0.196	hERG Blockers (10um):	0.572
Human Hepatotoxicity (H-HT):	0.641	Drug-induced Liver Injury (DILI):	0.737
AMES Toxicity:	0.685	Rat Oral Acute Toxicity:	0.53
Maximum Recommended Daily Dose:	0.516	Skin Sensitization:	0.194
Carcinogencity:	0.582	Eye Corrosion:	0.027
Eye Irritation:	0.964	Respiratory Toxicity:	0.669
Drug-induced Neurotoxicity:	0.799	Ototoxicity:	0.385
Hematotoxicity:	0.44	Drug-induced Nephrotoxicity:	0.451
Genotoxicity:	0.545	RPMI-8226 Immunitoxicity:	0.053
A549 Cytotoxicity:	0.177	Hek293 Cytotoxicity:	0.212
BCF:	1.41 ? 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:	4.378 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.619 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.572 ? 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
NPO21538	Fusarium sp.	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11076576]
NPO21538	Fusarium sp.	Species	Nectriaceae	Eukaryota	Melia azedarach	n.a.	n.a.	PMID[21353539]
NPO21538	Fusarium sp.	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24183988]
NPO21538	Fusarium sp.	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33180497]
NPO21538	Fusarium sp.	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8988601]
NPO21538	Fusarium sp.	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21538	Fusarium sp.	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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	1
EC50	2

Activity Type	# Activity
Individual protein	1
Organism	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6638	Individual protein	Pyruvate kinase	Staphylococcus aureus (strain MRSA252)	IC50	=	50200.0	nM	PMID[25266785]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT22368	Organism	Zika virus	Zika virus	EC50	=	5000.0	nM	PMID[33180497]
NPT22368	Organism	Zika virus	Zika virus	EC50	=	4200.0	nM	PMID[34438338]

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 NPC300149 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	38334
0.1-0.2	10198
0.2-0.3	867
0.3-0.4	295
0.4-0.5	118
0.5-0.6	30
0.6-0.7	6
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	NPC154339
0.6829	Remote Similarity	NPC267343
0.6667	Remote Similarity	NPC42372
0.6471	Remote Similarity	NPC261195
0.6216	Remote Similarity	NPC230002
0.6154	Remote Similarity	NPC138370
0.6	Remote Similarity	NPC72435
0.5946	Remote Similarity	NPC216643
0.5946	Remote Similarity	NPC288838
0.5946	Remote Similarity	NPC601214
0.5789	Remote Similarity	NPC105127
0.5789	Remote Similarity	NPC53947
0.5789	Remote Similarity	NPC102423
0.575	Remote Similarity	NPC230869
0.575	Remote Similarity	NPC279081
0.561	Remote Similarity	NPC276657
0.56	Remote Similarity	NPC476460
0.5581	Remote Similarity	NPC67288
0.5581	Remote Similarity	NPC310665
0.5556	Remote Similarity	NPC74413
0.55	Remote Similarity	NPC131718
0.55	Remote Similarity	NPC96102
0.549	Remote Similarity	NPC99939
0.5455	Remote Similarity	NPC603879
0.5385	Remote Similarity	NPC308931
0.5349	Remote Similarity	NPC111275
0.5238	Remote Similarity	NPC29886
0.5238	Remote Similarity	NPC601179
0.5238	Remote Similarity	NPC604154
0.5227	Remote Similarity	NPC605863
0.5217	Remote Similarity	NPC315555
0.5217	Remote Similarity	NPC55772
0.5217	Remote Similarity	NPC600736
0.5217	Remote Similarity	NPC602656
0.5217	Remote Similarity	NPC605085
0.5116	Remote Similarity	NPC84911
0.5116	Remote Similarity	NPC608908

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC300149 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5842
0.1-0.2	3119
0.2-0.3	153
0.3-0.4	28
0.4-0.5	7
0.5-0.6	1
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
0.55	Remote Similarity	NPD198	Clinical (unspecified phase)

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