NPASS Compound

Natural Product: NPC313133

Natural Product ID	NPC313133
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UVDQDNQWGQFIAO-AWEZNQCLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	10042806
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0000381] Aporphines

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 47 51 0 0 0 0 0 0 0 0999 V2000 -2.4588 -2.6050 -0.9868 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2663 -2.0982 0.3376 N 0 0 0 0 0 4 0 0 0 0 0 0 -3.5241 -1.5559 0.8216 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9859 -0.3959 0.0304 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9153 0.5975 -0.1355 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2092 1.9151 -0.4383 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2482 2.8654 -0.6188 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9055 2.5145 -0.4999 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6126 1.1938 -0.1984 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7985 0.7976 -0.2359 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7896 1.7412 -0.3066 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1201 1.3010 -0.2332 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4629 -0.0207 -0.0949 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4203 -0.9314 -0.0300 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1035 -0.5472 -0.0993 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0636 -1.5907 -0.1164 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2083 -1.1189 0.4473 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5936 0.2205 -0.0079 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7112 -2.2798 0.1098 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8154 -2.7779 1.4373 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7726 -0.4746 -0.0191 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8196 0.4518 -0.0854 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1729 3.6656 -0.7326 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0165 4.8085 -0.5946 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2819 4.2399 -0.9236 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7623 -3.4382 -1.1750 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4245 -1.8256 -1.7736 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4893 -3.0446 -1.0443 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0223 -2.8954 0.9622 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2440 -2.3974 0.8303 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3886 -1.2345 1.8936 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8804 0.0378 0.5244 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2468 -0.7439 -1.0106 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2573 2.1802 -0.5313 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6722 2.7876 -0.4069 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9313 2.0136 -0.2854 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0407 -1.8715 -1.2125 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3956 -2.4950 0.4530 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0125 -0.9869 1.5741 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8749 -2.8437 1.7741 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3171 -3.7651 1.4770 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3141 -2.0949 2.1712 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1043 0.7218 -1.1238 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6720 1.3471 0.5469 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7273 -0.0655 0.3419 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7325 5.6106 -1.2817 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9860 5.0873 0.4699 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 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 1 0 17 18 1 0 14 19 1 0 19 20 1 0 13 21 1 0 21 22 1 0 8 23 1 0 23 24 1 0 24 25 1 0 17 2 1 0 18 5 2 0 25 7 1 0 18 9 1 0 15 10 1 0 1 26 1 0 1 27 1 0 1 28 1 0 2 29 1 0 3 30 1 0 3 31 1 0 4 32 1 0 4 33 1 0 6 34 1 0 11 35 1 0 12 36 1 0 16 37 1 0 16 38 1 0 17 39 1 1 20 40 1 0 20 41 1 0 20 42 1 0 22 43 1 0 22 44 1 0 22 45 1 0 24 46 1 0 24 47 1 0 M CHG 1 2 1 M END

Standard InCHIKey	UVDQDNQWGQFIAO-AWEZNQCLSA-N
Standard InCHI	InChI=1S/C20H21NO4/c1-21-7-6-11-8-16-20(25-10-24-16)18-12-4-5-15(22-2)19(23-3)13(12)9-14(21)17(11)18/h4-5,8,14H,6-7,9-10H2,1-3H3/p+1/t14-/m0/s1
SMILES	C[NH+]1CCc2cc3c(c4-c5ccc(c(c5C[C@H]1c24)OC)OC)OCO3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	339.15	Volume:	342.033 ? Van der Waals volume.
Dense:	0.992	LogP:	2.639 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.656 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.792 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	24.0
TPSA:	40.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.84	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.195	Fsp³:	0.4
MCE-18:	87.286 ? 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:	0
Colloidal aggregators:	0.522	Fluc inhibitor:	0.065 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.763 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.314 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.004	Promiscuous compounds:	0.841

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.742	MDCK Permeability:	-4.717
Pgp-inhibitor:	0.217	Pgp-substrate:	0.084
PAMPA:	0.037 ? 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%):	0.117	30% Bioavailability (F30%):	0.032
50% Bioavailability (F50%):	0.949

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.997	MRP1:	0.865
Plasma Protein Binding (PPB):	79.371%	Volume Distribution (VD):	0.316
Fu:	22.931% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.939
OATP1B3 inhibitor:	0.962	BCRP inhibitor:	0.709
BSEP inhibitor:	0.86

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	0.015
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.705	CYP2C9-substrate:	0.985
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.864
CYP3A4-inhibitor:	0.994	CYP3A4-substrate:	0.978
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.456 ? 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):

5.978

Half-life (T1/2):

1.712

ADMET: Toxicity

hERG Blockers:	0.443	hERG Blockers (10um):	0.66
Human Hepatotoxicity (H-HT):	0.56	Drug-induced Liver Injury (DILI):	0.079
AMES Toxicity:	0.788	Rat Oral Acute Toxicity:	0.528
Maximum Recommended Daily Dose:	0.908	Skin Sensitization:	0.71
Carcinogencity:	0.874	Eye Corrosion:	0.001
Eye Irritation:	0.487	Respiratory Toxicity:	0.83
Drug-induced Neurotoxicity:	0.819	Ototoxicity:	0.471
Hematotoxicity:	0.209	Drug-induced Nephrotoxicity:	0.33
Genotoxicity:	0.48	RPMI-8226 Immunitoxicity:	0.078
A549 Cytotoxicity:	0.08	Hek293 Cytotoxicity:	0.423
BCF:	2.09 ? 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:	4.317 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.325 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.349 ? 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
NPO22181	Leibnitzia anandria	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24699147]
NPO21410	Populus balsamifera	Species	Salicaceae	Eukaryota	Buds	n.a.	n.a.	PMID[25927817]
NPO21410	Populus balsamifera	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38612781]
NPO18333	Sphaerophysa salsula	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22181	Leibnitzia anandria	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20325	Dictyodendrilla cavernosa	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19888	Doronicum grandiflorum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21780	Strychnos gossweileri	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21410	Populus balsamifera	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7002	Ardisia hortorum	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20965	Oxytropis lanata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5902	Stephania bancroftii	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20581	Sargassum fulvellum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21410	Populus balsamifera	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7002	Ardisia hortorum	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21410	Populus balsamifera	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7002	Ardisia hortorum	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22181	Leibnitzia anandria	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21410	Populus balsamifera	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7002	Ardisia hortorum	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22498	Lithocarpus haipinii	Species	Fagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19668.1	Euphorbia characias subsp. wulfenii	Subspecies	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22181	Leibnitzia anandria	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20581	Sargassum fulvellum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19888	Doronicum grandiflorum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22942	Moesziomyces antarcticus	Species	Ustilaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22629	Spongia vaginalis	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20704	Conus gladiator	Species	Conidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5902	Stephania bancroftii	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21410	Populus balsamifera	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20965	Oxytropis lanata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22436	Lora quadra	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO20325	Dictyodendrilla cavernosa	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21780	Strychnos gossweileri	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18333	Sphaerophysa salsula	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21468	Dilophus guineensis	Species	Dictyotaceae	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 NPC313133 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	34986
0.1-0.2	13813
0.2-0.3	994
0.3-0.4	53
0.4-0.5	7
0.5-0.6	3
0.6-0.7	2
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
0.7869	Intermediate Similarity	NPC225774
0.6613	Remote Similarity	NPC210918
0.625	Remote Similarity	NPC302527
0.5507	Remote Similarity	NPC304659
0.5507	Remote Similarity	NPC86144
0.5211	Remote Similarity	NPC149090

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC313133 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6355
0.1-0.2	2753
0.2-0.3	42
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