NPASS Compound

Natural Product: NPC295193

Natural Product ID	NPC295193
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AYDPSPGOURFSMI-OFNKIYASSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	46223683
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002665] Benzophenanthridine alkaloids [CHEMONTID:0002667] Dihydrobenzophenanthridine alkaloids

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 51 57 0 0 0 0 0 0 0 0999 V2000 -1.2323 4.2670 -0.2509 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4946 2.7878 -0.3667 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9981 2.0298 0.5856 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0936 0.6723 0.0815 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4609 -0.3640 0.9659 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7778 -1.7070 0.3589 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8939 -2.3418 -0.5032 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4116 -1.7602 -0.7116 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2609 -2.2699 -1.6524 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4711 -1.5984 -1.9256 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8044 -0.4365 -1.2591 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9645 0.2434 -1.5197 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2786 1.4084 -0.8668 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4062 1.9003 0.0656 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2037 1.2506 0.3765 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9249 0.0929 -0.2844 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7552 -0.5814 -0.0279 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0327 -0.1991 1.1057 N 0 0 0 0 0 0 0 0 0 0 0 0 0.6123 0.2324 2.3288 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9151 3.0644 0.5867 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2754 3.1367 0.1661 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3700 2.2513 -0.9590 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2230 -3.5482 -1.1099 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4531 -4.1025 -0.8317 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3294 -3.4762 0.0241 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0113 -2.2801 0.6284 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0580 -1.8610 1.4390 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8658 -3.0020 1.6511 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5997 -3.7878 0.4808 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6179 0.6936 -1.2100 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2327 1.9724 -1.5442 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7430 2.3794 -2.6569 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3346 4.7202 -1.2428 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1958 4.3756 0.1012 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9329 4.7364 0.4730 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2735 2.4161 1.5583 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1734 0.4030 0.0391 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9454 -0.3300 1.9396 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1155 -3.1410 -2.2254 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1649 -1.9633 -2.6514 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6283 -0.1956 -2.2794 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5268 1.7131 1.0454 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2395 1.1354 2.7921 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2237 -0.5563 3.0868 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6875 -0.0014 2.4163 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5404 4.1372 -0.2047 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9719 2.7353 0.9208 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5218 -3.9974 -1.7589 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6934 -5.0439 -1.3137 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6388 -3.5386 2.5744 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9251 -2.6713 1.5646 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 1 0 5 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 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 14 20 1 0 20 21 1 0 21 22 1 0 7 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 28 29 1 0 4 30 1 0 30 31 1 0 31 32 2 0 31 2 1 0 18 5 1 0 29 25 1 0 26 6 1 0 17 8 1 0 16 11 1 0 22 13 1 0 1 33 1 0 1 34 1 0 1 35 1 0 3 36 1 0 4 37 1 6 5 38 1 1 9 39 1 0 10 40 1 0 12 41 1 0 15 42 1 0 19 43 1 0 19 44 1 0 19 45 1 0 21 46 1 0 21 47 1 0 23 48 1 0 24 49 1 0 28 50 1 0 28 51 1 0 M END

Standard InCHIKey	AYDPSPGOURFSMI-OFNKIYASSA-N
Standard InCHI	InChI=1S/C25H19NO6/c1-12-7-20(32-25(12)27)23-21-14(5-6-17-24(21)31-11-28-17)15-4-3-13-8-18-19(30-10-29-18)9-16(13)22(15)26(23)2/h3-9,20,23H,10-11H2,1-2H3/t20-,23+/m1/s1
SMILES	CC1=C[C@H]([C@H]2c3c(-c4ccc5cc6c(cc5c4N2C)OCO6)ccc2c3OCO2)OC1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	429.12	Volume:	418.434 ? Van der Waals volume.
Dense:	1.026	LogP:	3.828 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.454 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.203 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	35.0
TPSA:	66.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	7.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.534	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.926	Fsp³:	0.24
MCE-18:	117.29 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.995	Fluc inhibitor:	0.749 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.701 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.584 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.012	Promiscuous compounds:	0.521

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.01	MDCK Permeability:	-4.714
Pgp-inhibitor:	0.987	Pgp-substrate:	0.167
PAMPA:	0.108 ? 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):	0.0
20% Bioavailability (F20%):	0.05	30% Bioavailability (F30%):	0.012
50% Bioavailability (F50%):	0.968

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.497	MRP1:	0.903
Plasma Protein Binding (PPB):	97.704%	Volume Distribution (VD):	0.053
Fu:	2.396% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.058
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.998
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.804
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.995
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.412	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.952	CYP2C8-inhibitor:	0.001
HLM stability:	0.956 ? 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):

3.51

Half-life (T1/2):

0.791

ADMET: Toxicity

hERG Blockers:	0.298	hERG Blockers (10um):	0.535
Human Hepatotoxicity (H-HT):	0.807	Drug-induced Liver Injury (DILI):	0.99
AMES Toxicity:	0.958	Rat Oral Acute Toxicity:	0.766
Maximum Recommended Daily Dose:	0.815	Skin Sensitization:	0.942
Carcinogencity:	0.963	Eye Corrosion:	0.0
Eye Irritation:	0.367	Respiratory Toxicity:	0.913
Drug-induced Neurotoxicity:	0.942	Ototoxicity:	0.661
Hematotoxicity:	0.92	Drug-induced Nephrotoxicity:	0.948
Genotoxicity:	0.952	RPMI-8226 Immunitoxicity:	0.345
A549 Cytotoxicity:	0.813	Hek293 Cytotoxicity:	0.704
BCF:	1.736 ? 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:	4.62 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.715 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.13 ? 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
NPO24024	Fusarium semitectum	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10978211]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	xylem	n.a.	PMID[14600386]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	fruits	n.a.	n.a.	PMID[15787435]
NPO24024	Fusarium semitectum	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22439674]
NPO18823	Colysis pothifolia	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26731047]
NPO24024	Fusarium semitectum	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20871	Pueraria tuberosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21004	Nicotiana plumbaginifolia	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18613	Commiphora erlangeriana	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13216	Streptomyces pulveraceus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20871	Pueraria tuberosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21004	Nicotiana plumbaginifolia	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20871	Pueraria tuberosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21004	Nicotiana plumbaginifolia	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20871	Pueraria tuberosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25619	Vitex divaricata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18823	Colysis pothifolia	Species	Polypodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24024	Fusarium semitectum	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19340	Orobanche caerulescens	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21143	Cryptocarya canelilla	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21004	Nicotiana plumbaginifolia	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13216	Streptomyces pulveraceus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO20871	Pueraria tuberosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21677	Liatris aspera	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18580	Diabelia spathulata	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21230	Heterodermia obscurata	Species	Physciaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18421	Tachardia lacca	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO15221	Crambe fruticosa	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8315	Wunderlichia crulsiana	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20271	Canarina canariensis	Species	Campanulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18613	Commiphora erlangeriana	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	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

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

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 NPC295193 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	19656
0.1-0.2	29448
0.2-0.3	743
0.3-0.4	3
0.4-0.5	2
0.5-0.6	7
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
0.5753	Remote Similarity	NPC193906
0.5753	Remote Similarity	NPC23080
0.5634	Remote Similarity	NPC481448
0.5541	Remote Similarity	NPC302001
0.5417	Remote Similarity	NPC162653
0.5352	Remote Similarity	NPC206442
0.5205	Remote Similarity	NPC487848

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC295193 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5321
0.1-0.2	3814
0.2-0.3	15
0.3-0.4	0
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