NPASS Compound

Natural Product: NPC185200

Natural Product ID	NPC185200
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KBMIVGVAJKVWBU-DEYYWGMASA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	164952
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0001213] Pyridoindoles [CHEMONTID:0001914] Beta carbolines

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 48 51 0 0 0 0 0 0 0 0999 V2000 -4.0320 2.4066 -0.2813 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6776 1.1532 0.4496 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2072 0.7787 0.2618 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4241 1.9281 0.8033 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0419 1.6297 0.7417 N 0 0 0 0 0 0 0 0 0 0 0 0 0.6969 2.0773 -0.3647 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1889 1.9937 0.0023 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4366 0.5321 0.1236 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4215 -0.2770 -0.3810 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5178 -0.0359 -1.1595 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3553 -1.0722 -1.5227 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0490 -2.3458 -1.0763 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9405 -2.5742 -0.2920 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0931 -1.5516 0.0803 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9639 -1.4698 0.8197 N 0 0 0 0 0 0 0 0 0 0 0 0 1.5273 -0.1814 0.8672 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3964 0.5295 1.4966 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7027 -0.4090 1.9243 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8513 -0.4793 0.9635 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6242 -1.6020 -0.0406 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8514 -1.8730 -0.8734 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6391 -2.9053 -1.7857 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1389 2.4005 -0.4392 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8236 3.3304 0.2996 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5887 2.4643 -1.3086 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9220 1.2965 1.5109 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2909 0.3253 0.0550 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9967 0.6462 -0.8327 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7030 2.0261 1.8921 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6057 2.8800 0.2621 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5988 1.4544 -1.2837 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4355 3.1280 -0.5948 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2899 2.5311 0.9560 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8068 2.4698 -0.7784 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7834 0.9546 -1.5250 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2289 -0.8952 -2.1402 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6655 -3.2073 -1.3249 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7172 -3.5674 0.0457 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5030 -2.2796 1.2814 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8205 0.9413 2.4651 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0865 -0.1600 2.9321 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2555 -1.4193 2.0009 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7737 -0.8031 1.5338 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7588 -1.4287 -0.6782 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4741 -2.5261 0.5915 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0380 -0.9670 -1.5085 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7259 -2.1566 -0.2574 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2035 -3.6903 -1.6269 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 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 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 21 22 1 0 19 3 1 0 17 5 1 0 16 8 2 0 14 9 1 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 2 27 1 0 3 28 1 6 4 29 1 0 4 30 1 0 6 31 1 0 6 32 1 0 7 33 1 0 7 34 1 0 10 35 1 0 11 36 1 0 12 37 1 0 13 38 1 0 15 39 1 0 17 40 1 1 18 41 1 0 18 42 1 0 19 43 1 1 20 44 1 0 20 45 1 0 21 46 1 0 21 47 1 0 22 48 1 0 M END

Standard InCHIKey	KBMIVGVAJKVWBU-DEYYWGMASA-N
Standard InCHI	InChI=1S/C19H26N2O/c1-2-13-12-21-9-7-16-15-5-3-4-6-17(15)20-19(16)18(21)11-14(13)8-10-22/h3-6,13-14,18,20,22H,2,7-12H2,1H3/t13-,14-,18-/m0/s1
SMILES	CC[C@H]1CN2CCc3c4ccccc4[nH]c3[C@@H]2C[C@@H]1CCO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	298.2	Volume:	323.192 ? Van der Waals volume.
Dense:	0.923	LogP:	2.518 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.46 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.123 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	20.0
TPSA:	39.26 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.91	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.513	Fsp³:	0.579
MCE-18:	69.333 ? 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:	0.38	Fluc inhibitor:	0.073 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.673 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.089 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.003	Promiscuous compounds:	0.309

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.99	MDCK Permeability:	-4.983
Pgp-inhibitor:	0.046	Pgp-substrate:	0.969
PAMPA:	0.026 ? 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):	0.001
20% Bioavailability (F20%):	0.427	30% Bioavailability (F30%):	0.745
50% Bioavailability (F50%):	0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.833	MRP1:	0.963
Plasma Protein Binding (PPB):	70.493%	Volume Distribution (VD):	-0.012
Fu:	22.323% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.279
OATP1B3 inhibitor:	0.312	BCRP inhibitor:	0.914
BSEP inhibitor:	0.979

ADMET: Metabolism

CYP1A2-inhibitor:	0.902	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.031	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.996
CYP2D6-inhibitor:	0.98	CYP2D6-substrate:	0.053
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.831
HLM stability:	0.003 ? 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):

11.253

Half-life (T1/2):

1.709

ADMET: Toxicity

hERG Blockers:	0.668	hERG Blockers (10um):	0.62
Human Hepatotoxicity (H-HT):	0.62	Drug-induced Liver Injury (DILI):	0.135
AMES Toxicity:	0.456	Rat Oral Acute Toxicity:	0.689
Maximum Recommended Daily Dose:	0.912	Skin Sensitization:	0.926
Carcinogencity:	0.659	Eye Corrosion:	0.005
Eye Irritation:	0.669	Respiratory Toxicity:	0.988
Drug-induced Neurotoxicity:	0.785	Ototoxicity:	0.368
Hematotoxicity:	0.159	Drug-induced Nephrotoxicity:	0.849
Genotoxicity:	0.305	RPMI-8226 Immunitoxicity:	0.049
A549 Cytotoxicity:	0.496	Hek293 Cytotoxicity:	0.519
BCF:	1.444 ? 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:	3.68 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.211 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.528 ? 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
NPO15819	Hunteria zeylanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19388660]
NPO15819	Hunteria zeylanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21524573]
NPO15819	Hunteria zeylanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28362501]
NPO15819	Hunteria zeylanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15819	Hunteria zeylanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15819	Hunteria zeylanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15819	Hunteria zeylanica	Species	Apocynaceae	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 NPC185200 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	33042
0.1-0.2	15781
0.2-0.3	818
0.3-0.4	134
0.4-0.5	46
0.5-0.6	19
0.6-0.7	18
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
0.6944	Remote Similarity	NPC486452
0.6944	Remote Similarity	NPC74591
0.6812	Remote Similarity	NPC165441
0.6667	Remote Similarity	NPC611453
0.6522	Remote Similarity	NPC229173
0.6184	Remote Similarity	NPC486449
0.6184	Remote Similarity	NPC63199
0.6184	Remote Similarity	NPC313985
0.6184	Remote Similarity	NPC249150
0.6184	Remote Similarity	NPC111602
0.6184	Remote Similarity	NPC102338
0.6184	Remote Similarity	NPC196251
0.6184	Remote Similarity	NPC33619
0.6104	Remote Similarity	NPC81654
0.6104	Remote Similarity	NPC50503
0.6104	Remote Similarity	NPC607669
0.6027	Remote Similarity	NPC482948
0.6	Remote Similarity	NPC88097
0.5974	Remote Similarity	NPC486443
0.5974	Remote Similarity	NPC486446
0.5915	Remote Similarity	NPC21174
0.589	Remote Similarity	NPC474897
0.5775	Remote Similarity	NPC317430
0.5696	Remote Similarity	NPC175474
0.5696	Remote Similarity	NPC99921
0.557	Remote Similarity	NPC483467
0.5375	Remote Similarity	NPC273374
0.5366	Remote Similarity	NPC312870
0.5366	Remote Similarity	NPC199851
0.5366	Remote Similarity	NPC294909
0.5366	Remote Similarity	NPC254240
0.5366	Remote Similarity	NPC128265
0.5366	Remote Similarity	NPC604675
0.5256	Remote Similarity	NPC284645
0.5122	Remote Similarity	NPC107782
0.5122	Remote Similarity	NPC486454
0.5067	Remote Similarity	NPC271797

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC185200 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5396
0.1-0.2	3610
0.2-0.3	131
0.3-0.4	7
0.4-0.5	2
0.5-0.6	2
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	Drug ID	Developmental Stage
0.6184	Remote Similarity	NPD4601	Phase 4
0.6104	Remote Similarity	NPD4600	Approved
0.5366	Remote Similarity	NPD4500	Approved
0.5366	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