NPASS Compound

Natural Product: NPC540096

Natural Product ID	NPC540096
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	methyl (1~{R},15~{S},18~{S},19~{S},20~{R})-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate
IUPAC Name	methyl (1~{R},15~{S},18~{S},19~{S},20~{R})-18-hydroxy-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 52 56 0 0 0 0 0 0 0 0999 V2000 -4.6089 3.4809 -0.3900 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3231 2.0942 -0.5288 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1449 1.5360 -0.0285 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3614 2.3140 0.5431 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9404 0.1036 -0.2193 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6615 -0.4529 0.3296 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4617 0.4073 0.1514 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7932 -0.4191 0.2964 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0194 0.3794 0.2784 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2163 -0.2834 0.0972 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1058 -1.7772 -0.0633 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0001 -1.9976 -1.0785 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7482 -1.4516 -0.6947 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.1911 -2.4467 -0.1931 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5463 -1.8444 -0.2507 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6240 -2.6942 0.3611 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9547 -2.1366 -0.1543 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0838 -0.7297 0.3365 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2974 -0.1601 0.0246 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2555 0.5982 0.1055 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6156 0.4409 -0.0327 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4614 1.5143 0.0145 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9102 2.7591 0.2047 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5304 2.9280 0.3460 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6773 1.8498 0.2989 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3536 1.6779 0.3964 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.6183 3.6478 -0.8195 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6414 3.8043 0.6619 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8936 4.0443 -1.0143 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9369 -0.1038 -1.3255 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8198 -0.5972 1.4374 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4585 0.9973 -0.7733 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4324 1.1290 1.0201 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7417 -0.9231 1.2987 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0270 -2.2110 -0.4629 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7582 -2.2415 0.8836 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3343 -1.4884 -2.0174 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9059 -3.0735 -1.2906 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1351 -2.6923 0.8358 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1496 -3.3029 -0.8703 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8165 -1.7375 -1.3422 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6284 -2.5685 1.4623 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4874 -3.7406 0.0400 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8035 -2.7695 0.1098 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8786 -2.1382 -1.2709 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9647 -0.7358 1.4500 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7194 0.2685 0.8338 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9994 -0.5576 -0.1801 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5201 1.3455 -0.0983 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5732 3.6186 0.2438 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1219 3.9074 0.4934 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6444 2.4288 0.5445 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 10 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 18 5 1 0 25 20 1 0 15 6 1 0 13 8 1 0 26 9 1 0 1 27 1 0 1 28 1 0 1 29 1 0 5 30 1 6 6 31 1 1 7 32 1 0 7 33 1 0 8 34 1 1 11 35 1 0 11 36 1 0 12 37 1 0 12 38 1 0 14 39 1 0 14 40 1 0 15 41 1 6 16 42 1 0 16 43 1 0 17 44 1 0 17 45 1 0 18 46 1 1 19 47 1 0 21 48 1 0 22 49 1 0 23 50 1 0 24 51 1 0 26 52 1 0 M END

Standard InCHIKey	BLGXFZZNTVWLAY-HJLQZSMCSA-N
Standard InCHI	InChI=1S/C21H26N2O3/c1-26-21(25)19-15-10-17-20-14(13-4-2-3-5-16(13)22-20)8-9-23(17)11-12(15)6-7-18(19)24/h2-5,12,15,17-19,22,24H,6-11H2,1H3/t12-,15-,17-,18+,19+/m1/s1
SMILES	COC(=O)[C@H]1[C@@H]2C[C@@H]3C4=C(CCN3C[C@H]2CC[C@@H]1O)C1=CC=CC=C1N4

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.19	Volume:	364.172 ? Van der Waals volume.
Dense:	0.973	LogP:	2.201 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.272 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.529 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	26.0
TPSA:	65.56 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.773	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.875	Fsp³:	0.571
MCE-18:	95.333 ? 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:	0.329	Fluc inhibitor:	0.007 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.71 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.013 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.823

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.419	MDCK Permeability:	-5.123
Pgp-inhibitor:	0.344	Pgp-substrate:	0.98
PAMPA:	0.006 ? 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%):	0.285	30% Bioavailability (F30%):	0.75
50% Bioavailability (F50%):	0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.723	MRP1:	0.97
Plasma Protein Binding (PPB):	70.438%	Volume Distribution (VD):	0.12
Fu:	27.79% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.347
OATP1B3 inhibitor:	0.416	BCRP inhibitor:	0.908
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.362	CYP1A2-substrate:	0.029
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.938
CYP2D6-inhibitor:	0.798	CYP2D6-substrate:	0.018
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.139
HLM stability:	0.009 ? 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):

10.013

Half-life (T1/2):

1.962

ADMET: Toxicity

hERG Blockers:	0.648	hERG Blockers (10um):	0.576
Human Hepatotoxicity (H-HT):	0.517	Drug-induced Liver Injury (DILI):	0.17
AMES Toxicity:	0.646	Rat Oral Acute Toxicity:	0.769
Maximum Recommended Daily Dose:	0.971	Skin Sensitization:	0.937
Carcinogencity:	0.633	Eye Corrosion:	0.0
Eye Irritation:	0.253	Respiratory Toxicity:	0.978
Drug-induced Neurotoxicity:	0.63	Ototoxicity:	0.181
Hematotoxicity:	0.131	Drug-induced Nephrotoxicity:	0.831
Genotoxicity:	0.934	RPMI-8226 Immunitoxicity:	0.046
A549 Cytotoxicity:	0.527	Hek293 Cytotoxicity:	0.57
BCF:	0.644 ? 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:	3.469 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.154 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.408 ? 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
NPO53001	Rauwolfia sprucei Muell.	n.a.	n.a.	n.a.	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 NPC540096 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	17315
0.1-0.2	31426
0.2-0.3	863
0.3-0.4	167
0.4-0.5	51
0.5-0.6	19
0.6-0.7	12
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC313985
1.0	High Similarity	NPC249150
1.0	High Similarity	NPC33619
0.9851	High Similarity	NPC81654
0.7467	Intermediate Similarity	NPC486452
0.7467	Intermediate Similarity	NPC74591
0.6923	Remote Similarity	NPC486443
0.6923	Remote Similarity	NPC486446
0.642	Remote Similarity	NPC50503
0.642	Remote Similarity	NPC607669
0.6296	Remote Similarity	NPC486449
0.6296	Remote Similarity	NPC63199
0.6296	Remote Similarity	NPC111602
0.6296	Remote Similarity	NPC102338
0.6296	Remote Similarity	NPC196251
0.6184	Remote Similarity	NPC185200
0.6024	Remote Similarity	NPC175474
0.6024	Remote Similarity	NPC99921
0.5904	Remote Similarity	NPC273374
0.5851	Remote Similarity	NPC191489
0.5714	Remote Similarity	NPC483467
0.5698	Remote Similarity	NPC312870
0.5698	Remote Similarity	NPC199851
0.5698	Remote Similarity	NPC294909
0.5698	Remote Similarity	NPC254240
0.5698	Remote Similarity	NPC128265
0.5698	Remote Similarity	NPC604675
0.5465	Remote Similarity	NPC107782
0.5465	Remote Similarity	NPC486454
0.5443	Remote Similarity	NPC21174
0.5375	Remote Similarity	NPC229173
0.5244	Remote Similarity	NPC165441
0.5116	Remote Similarity	NPC220151
0.5116	Remote Similarity	NPC19692
0.5067	Remote Similarity	NPC88097
0.506	Remote Similarity	NPC474897
0.5056	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 NPC540096 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3881
0.1-0.2	5086
0.2-0.3	170
0.3-0.4	4
0.4-0.5	4
0.5-0.6	3
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	2

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD4601	Phase 4
0.9851	High Similarity	NPD4600	Approved
0.5851	Remote Similarity	NPD7708	Phase 4
0.5698	Remote Similarity	NPD4500	Approved
0.5698	Remote Similarity	NPD4501	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