NPASS Compound

Natural Product: NPC578730

Natural Product ID	NPC578730
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	methyl (1~{S},15~{R},18~{S},19~{R},20~{R})-18-acetoxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate
IUPAC Name	methyl (1~{S},15~{R},18~{S},19~{R},20~{R})-18-acetoxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 57 61 0 0 0 0 0 0 0 0999 V2000 -2.3708 -1.0769 -3.0162 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9490 -0.1777 -2.0406 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5854 0.0584 -0.8346 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6245 -0.6475 -0.7007 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2262 0.9542 0.2144 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8947 0.7752 0.8929 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2566 1.2945 0.1012 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0496 0.2912 -0.6399 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5063 0.3439 -0.3465 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2604 -0.6849 -0.8642 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6538 -1.7918 -1.6750 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1938 -1.9948 -1.3623 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6487 -1.0483 -0.4938 N 0 0 0 0 0 0 0 0 0 0 0 0 0.1804 -1.5016 0.7512 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6925 -0.5597 1.5144 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9786 -1.2407 1.8882 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1806 -0.4308 2.0125 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2555 0.8702 1.3180 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5226 1.1109 0.7088 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2684 2.2507 1.0293 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5829 2.5367 0.4220 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7415 3.0284 1.8798 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5562 -0.4316 -0.4718 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7183 -1.1414 -0.7142 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8866 -0.6367 -0.1852 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9164 0.5239 0.5562 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7669 1.2295 0.7983 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5838 0.7308 0.2704 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3079 1.1828 0.3289 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4651 -1.6114 -3.4020 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0461 -1.8707 -2.6389 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8457 -0.6158 -3.8913 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2117 2.0171 -0.1720 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9782 1.5210 1.7436 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1673 2.0913 -0.5825 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9985 1.8770 0.7290 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9739 0.5384 -1.7436 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8110 -1.5712 -2.7404 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2156 -2.7336 -1.4658 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6440 -2.0492 -2.3447 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0492 -3.0229 -0.9164 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0756 -1.8709 1.3275 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3943 -2.4523 0.5465 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1429 -0.3997 2.4952 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8373 -1.8351 2.8426 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1414 -2.0641 1.1282 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4252 -0.2368 3.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0738 -1.0357 1.6655 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0149 1.7077 2.0344 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8296 3.6057 0.6477 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6087 2.4229 -0.6637 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4036 1.9344 0.8759 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6748 -2.0535 -1.3004 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8109 -1.1787 -0.3637 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8712 0.8645 0.9430 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8086 2.1413 1.3839 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0400 2.0636 0.8397 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 3 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 2 0 10 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 18 5 1 0 28 23 1 0 15 6 1 0 13 8 1 0 29 9 1 0 1 30 1 0 1 31 1 0 1 32 1 0 5 33 1 6 6 34 1 1 7 35 1 0 7 36 1 0 8 37 1 6 11 38 1 0 11 39 1 0 12 40 1 0 12 41 1 0 14 42 1 0 14 43 1 0 15 44 1 1 16 45 1 0 16 46 1 0 17 47 1 0 17 48 1 0 18 49 1 1 21 50 1 0 21 51 1 0 21 52 1 0 24 53 1 0 25 54 1 0 26 55 1 0 27 56 1 0 29 57 1 0 M END

Standard InCHIKey	AVICMXMDDSGUEL-XPVMQVPNSA-N
Standard InCHI	InChI=1S/C23H28N2O4/c1-13(26)29-20-8-7-14-12-25-10-9-16-15-5-3-4-6-18(15)24-22(16)19(25)11-17(14)21(20)23(27)28-2/h3-6,14,17,19-21,24H,7-12H2,1-2H3/t14-,17+,19-,20-,21+/m0/s1
SMILES	COC(=O)[C@@H]1[C@@H]2C[C@H]3C4=C(CCN3C[C@@H]2CC[C@@H]1OC(C)=O)C1=CC=CC=C1N4

Calculated Properties

Physi-Chem Properties

Molecular Weight:	396.2	Volume:	404.917 ? Van der Waals volume.
Dense:	0.978	LogP:	2.729 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.677 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.775 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	27.0
TPSA:	71.63 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.789	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.955	Fsp³:	0.565
MCE-18:	97.5 ? 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:	0.251	Fluc inhibitor:	0.008 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.54 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.015 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.938

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.408	MDCK Permeability:	-4.906
Pgp-inhibitor:	0.001	Pgp-substrate:	0.447
PAMPA:	0.212 ? 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%):	0.196	30% Bioavailability (F30%):	0.376
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.913	MRP1:	0.997
Plasma Protein Binding (PPB):	86.344%	Volume Distribution (VD):	0.132
Fu:	13.341% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.969
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.481
BSEP inhibitor:	0.94

ADMET: Metabolism

CYP1A2-inhibitor:	0.26	CYP1A2-substrate:	0.015
CYP2C19-inhibitor:	0.987	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.997
CYP2D6-inhibitor:	0.167	CYP2D6-substrate:	0.027
CYP3A4-inhibitor:	0.941	CYP3A4-substrate:	0.216
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.555 ? 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):

6.058

Half-life (T1/2):

0.932

ADMET: Toxicity

hERG Blockers:	0.37	hERG Blockers (10um):	0.516
Human Hepatotoxicity (H-HT):	0.473	Drug-induced Liver Injury (DILI):	0.239
AMES Toxicity:	0.655	Rat Oral Acute Toxicity:	0.701
Maximum Recommended Daily Dose:	0.889	Skin Sensitization:	0.974
Carcinogencity:	0.651	Eye Corrosion:	0.001
Eye Irritation:	0.327	Respiratory Toxicity:	0.935
Drug-induced Neurotoxicity:	0.684	Ototoxicity:	0.405
Hematotoxicity:	0.174	Drug-induced Nephrotoxicity:	0.61
Genotoxicity:	0.907	RPMI-8226 Immunitoxicity:	0.044
A549 Cytotoxicity:	0.222	Hek293 Cytotoxicity:	0.46
BCF:	0.669 ? 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:	3.515 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.995 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.499 ? 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
NPO43828	Aspidosperma excelsum Benth.	Genus	Apocynaceae	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

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 NPC578730 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	21370
0.1-0.2	27415
0.2-0.3	842
0.3-0.4	152
0.4-0.5	41
0.5-0.6	19
0.6-0.7	16
0.7-0.8	2
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
0.7089	Intermediate Similarity	NPC313985
0.7089	Intermediate Similarity	NPC249150
0.7089	Intermediate Similarity	NPC33619
0.7	Intermediate Similarity	NPC81654
0.6962	Remote Similarity	NPC486452
0.6962	Remote Similarity	NPC74591
0.6265	Remote Similarity	NPC486449
0.6265	Remote Similarity	NPC63199
0.6265	Remote Similarity	NPC111602
0.6265	Remote Similarity	NPC102338
0.6265	Remote Similarity	NPC486443
0.6265	Remote Similarity	NPC486446
0.6265	Remote Similarity	NPC196251
0.617	Remote Similarity	NPC191489
0.6047	Remote Similarity	NPC312870
0.6047	Remote Similarity	NPC199851
0.6047	Remote Similarity	NPC294909
0.6047	Remote Similarity	NPC254240
0.6047	Remote Similarity	NPC128265
0.6047	Remote Similarity	NPC604675
0.575	Remote Similarity	NPC185200
0.5698	Remote Similarity	NPC273374
0.5632	Remote Similarity	NPC175474
0.5632	Remote Similarity	NPC99921
0.5455	Remote Similarity	NPC107782
0.5455	Remote Similarity	NPC486454
0.5432	Remote Similarity	NPC21174
0.5281	Remote Similarity	NPC50503
0.5281	Remote Similarity	NPC607669
0.52	Remote Similarity	NPC100734
0.52	Remote Similarity	NPC88923
0.52	Remote Similarity	NPC315634
0.5181	Remote Similarity	NPC229173
0.5169	Remote Similarity	NPC483467
0.5146	Remote Similarity	NPC284685
0.5114	Remote Similarity	NPC220151
0.5114	Remote Similarity	NPC19692
0.5059	Remote Similarity	NPC474897
0.5055	Remote Similarity	NPC611453

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC578730 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4130
0.1-0.2	4852
0.2-0.3	153
0.3-0.4	6
0.4-0.5	1
0.5-0.6	3
0.6-0.7	3
0.7-0.8	2
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
0.7089	Intermediate Similarity	NPD4601	Phase 4
0.7	Intermediate Similarity	NPD4600	Approved
0.617	Remote Similarity	NPD7708	Phase 4
0.6047	Remote Similarity	NPD4500	Approved
0.6047	Remote Similarity	NPD4501	Approved
0.52	Remote Similarity	NPD7803	Phase 4
0.5146	Remote Similarity	NPD7955	Phase 4
0.5146	Remote Similarity	NPD7956	Approved

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