NPASS Compound

Natural Product: NPC330009

Natural Product ID	NPC330009
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GFEUNVMURRUASI-NBEPNCHPSA-N
IUPAC Name	n.a.
Synonyms	11-Hydroxycoronaridine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL517789
PubChem CID	44566751
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002748] Ibogan-type 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 2D 52 56 0 0 0 0 0 0 0 0999 V2000 3.0881 2.8728 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0788 3.9825 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0696 5.0922 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5008 6.4801 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9857 6.6815 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9033 5.4949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3344 4.1069 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.1520 3.9056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9214 2.6179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2452 5.8241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4153 2.7523 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1228 1.4297 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0459 4.1134 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5398 4.2478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2841 1.5763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4186 3.0703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 -1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 -3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 -3.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 -2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0967 -5.1517 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2251 1.8944 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9784 1.8635 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4090 3.5835 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9114 5.2302 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2463 2.7347 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4259 5.7328 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9664 6.7993 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2587 7.9605 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5545 8.0694 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9125 6.6046 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2596 4.8542 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6429 5.1776 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0370 7.0981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6373 5.2656 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0338 4.3823 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4054 5.7418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6743 2.7539 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7760 0.0000 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8112 0.1720 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7840 1.5950 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8911 2.7841 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3392 4.2546 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5736 -1.2902 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9499 -4.2246 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 -3.1443 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3299 -5.6152 0.0000 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 9 11 1 6 11 12 2 0 11 13 1 0 13 14 1 0 9 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 18 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 8 3 1 0 19 15 2 0 10 5 1 0 25 17 1 0 21 7 1 0 1 27 1 0 1 28 1 0 1 29 1 0 2 30 1 0 2 31 1 0 3 32 1 1 4 33 1 0 4 34 1 0 5 35 1 6 6 36 1 0 6 37 1 0 8 38 1 6 10 39 1 0 10 40 1 0 14 41 1 0 14 42 1 0 14 43 1 0 16 44 1 0 20 45 1 0 20 46 1 0 21 47 1 0 21 48 1 0 22 49 1 0 23 50 1 0 25 51 1 0 26 52 1 0 M END

Standard InCHIKey	GFEUNVMURRUASI-NBEPNCHPSA-N
Standard InCHI	InChI=1S/C21H26N2O3/c1-3-13-8-12-10-21(20(25)26-2)18-16(6-7-23(11-12)19(13)21)15-5-4-14(24)9-17(15)22-18/h4-5,9,12-13,19,22,24H,3,6-8,10-11H2,1-2H3/t12-,13-,19-,21+/m0/s1
SMILES	CC[C@H]1C[C@@H]2CN3[C@@H]1[C@](C2)(C(=O)OC)c1[nH]c2c(c1CC3)ccc(c2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.19	Volume:	364.172 ? Van der Waals volume.
Dense:	0.973	LogP:	2.772 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.873 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.873 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	65.56 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.814	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.176	Fsp³:	0.571
MCE-18:	99.273 ? 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:	0.285	Fluc inhibitor:	0.052 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.681 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.274 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.624

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.396	MDCK Permeability:	-5.231
Pgp-inhibitor:	0.002	Pgp-substrate:	0.851
PAMPA:	0.049 ? 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%):	0.459	30% Bioavailability (F30%):	0.757
50% Bioavailability (F50%):	0.946

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.354	MRP1:	0.991
Plasma Protein Binding (PPB):	81.497%	Volume Distribution (VD):	0.384
Fu:	21.167% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.358
OATP1B3 inhibitor:	0.523	BCRP inhibitor:	0.508
BSEP inhibitor:	0.729

ADMET: Metabolism

CYP1A2-inhibitor:	0.791	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.975	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.888
CYP2D6-inhibitor:	0.713	CYP2D6-substrate:	0.962
CYP3A4-inhibitor:	0.933	CYP3A4-substrate:	0.077
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.866
HLM stability:	0.869 ? 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):

10.853

Half-life (T1/2):

1.539

ADMET: Toxicity

hERG Blockers:	0.53	hERG Blockers (10um):	0.639
Human Hepatotoxicity (H-HT):	0.629	Drug-induced Liver Injury (DILI):	0.666
AMES Toxicity:	0.672	Rat Oral Acute Toxicity:	0.798
Maximum Recommended Daily Dose:	0.922	Skin Sensitization:	0.954
Carcinogencity:	0.599	Eye Corrosion:	0.001
Eye Irritation:	0.394	Respiratory Toxicity:	0.981
Drug-induced Neurotoxicity:	0.861	Ototoxicity:	0.487
Hematotoxicity:	0.375	Drug-induced Nephrotoxicity:	0.781
Genotoxicity:	0.919	RPMI-8226 Immunitoxicity:	0.115
A549 Cytotoxicity:	0.66	Hek293 Cytotoxicity:	0.846
BCF:	1.257 ? 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:	4.156 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.2 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.889 ? 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
NPO32495	tabernaemontana calcarea	Species	Apocynaceae	Eukaryota	n.a.	Madagascar rainforest	n.a.	PMID[12713407]

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

Activity Type	# Activity
Cell line	1

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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	4.8	ug.mL-1	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 NPC330009 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	17821
0.1-0.2	31176
0.2-0.3	730
0.3-0.4	85
0.4-0.5	20
0.5-0.6	14
0.6-0.7	6
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
0.7838	Intermediate Similarity	NPC469928
0.7534	Intermediate Similarity	NPC329858
0.7333	Intermediate Similarity	NPC473041
0.6795	Remote Similarity	NPC96321
0.6795	Remote Similarity	NPC111993
0.6582	Remote Similarity	NPC485936
0.6582	Remote Similarity	NPC485937
0.6456	Remote Similarity	NPC482061
0.642	Remote Similarity	NPC473105
0.5952	Remote Similarity	NPC474192
0.5647	Remote Similarity	NPC485887
0.5446	Remote Similarity	NPC485963
0.5412	Remote Similarity	NPC485938
0.5402	Remote Similarity	NPC485941
0.5221	Remote Similarity	NPC605382
0.5189	Remote Similarity	NPC17437
0.514	Remote Similarity	NPC485933
0.514	Remote Similarity	NPC485970
0.5135	Remote Similarity	NPC485960
0.5114	Remote Similarity	NPC485884
0.5094	Remote Similarity	NPC485969
0.5093	Remote Similarity	NPC475666
0.5054	Remote Similarity	NPC485947

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC330009 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3708
0.1-0.2	5297
0.2-0.3	138
0.3-0.4	5
0.4-0.5	1
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