NPASS Compound

Natural Product: NPC317999

Natural Product ID	NPC317999
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BNZYDQIAPCVNAT-VURMDHGXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5282941
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000262] Fatty acids and conjugates [CHEMONTID:0002949] Long-chain fatty acids

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 55 54 0 0 0 0 0 0 0 0999 V2000 -7.9156 1.5583 1.3342 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8759 1.3154 0.2455 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7619 -0.1894 0.1209 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7767 -0.5313 -0.9370 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4148 0.0275 -0.6275 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9447 -0.5187 0.6488 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8687 -1.2301 0.8076 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9384 -1.6114 -0.2519 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5840 -1.0119 0.1424 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4732 -1.3359 -0.8787 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7634 -0.6898 -0.3784 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9004 -0.9335 -1.3013 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1666 -0.2756 -0.7127 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0324 1.1926 -0.5445 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1794 1.9914 -0.1042 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8670 1.8171 1.1637 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5512 0.5145 1.3908 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5846 0.2542 0.3566 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9041 1.0298 -0.5667 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2769 -0.9654 0.4004 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6200 -2.6819 -1.0962 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4429 1.4001 2.3254 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6996 0.7857 1.1937 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3253 2.5777 1.2304 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2741 1.7697 -0.6777 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9234 1.8005 0.4989 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7493 -0.6156 -0.2253 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4760 -0.6276 1.0939 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1463 -0.1950 -1.9416 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7554 -1.6467 -1.0185 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7457 -0.2975 -1.4476 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4362 1.1542 -0.6213 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5877 -0.2718 1.5342 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6533 -1.5702 1.8530 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8579 -2.7329 -0.2674 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2564 -1.2737 -1.2271 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7285 0.0743 0.2325 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3146 -1.4647 1.1105 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1958 -0.8545 -1.8373 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0150 -1.0770 0.6244 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5812 0.4104 -0.2708 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1426 -2.0357 -1.2850 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7418 -0.5858 -2.3285 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1739 -0.7055 0.3454 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0740 -0.6003 -1.2249 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1756 1.4384 0.1543 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6798 1.5840 -1.5575 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9157 1.9941 -0.9908 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8252 3.1058 -0.1267 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6993 2.6030 1.2962 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2042 2.0761 2.0569 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8784 -0.3288 1.5599 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1422 0.6269 2.3989 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8146 -1.2486 -0.4070 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1252 -2.9950 -1.6668 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 3 7 8 1 0 8 9 1 0 9 10 1 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 2 0 18 20 1 0 10 21 1 0 1 22 1 0 1 23 1 0 1 24 1 0 2 25 1 0 2 26 1 0 3 27 1 0 3 28 1 0 4 29 1 0 4 30 1 0 5 31 1 0 5 32 1 0 6 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 11 40 1 0 11 41 1 0 12 42 1 0 12 43 1 0 13 44 1 0 13 45 1 0 14 46 1 0 14 47 1 0 15 48 1 0 15 49 1 0 16 50 1 0 16 51 1 0 17 52 1 0 17 53 1 0 20 54 1 0 21 55 1 0 M END

Standard InCHIKey	BNZYDQIAPCVNAT-VURMDHGXSA-N
Standard InCHI	InChI=1S/C18H34O3/c1-2-3-4-5-6-8-11-14-17(19)15-12-9-7-10-13-16-18(20)21/h6,8,17,19H,2-5,7,9-16H2,1H3,(H,20,21)/b8-6-
SMILES	CCCCCC=CCCC(CCCCCCCC(=O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	298.25	Volume:	340.982 ? Van der Waals volume.
Dense:	0.875	LogP:	5.425 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.26 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.271 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	2.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.327	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.708	Fsp³:	0.833
MCE-18:	2.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.017	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.01 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.986	Promiscuous compounds:	0.478

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.166	MDCK Permeability:	-4.727
Pgp-inhibitor:	0.0	Pgp-substrate:	0.103
PAMPA:	0.755 ? 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):	0.827
20% Bioavailability (F20%):	0.589	30% Bioavailability (F30%):	0.949
50% Bioavailability (F50%):	0.694

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.057	MRP1:	0.976
Plasma Protein Binding (PPB):	91.243%	Volume Distribution (VD):	-0.116
Fu:	6.885% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.043
OATP1B3 inhibitor:	0.947	BCRP inhibitor:	0.15
BSEP inhibitor:	0.198

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.19
CYP2C19-inhibitor:	0.886	CYP2C19-substrate:	0.458
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.085
CYP2D6-inhibitor:	0.741	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.031 ? 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):

3.904

Half-life (T1/2):

0.702

ADMET: Toxicity

hERG Blockers:	0.154	hERG Blockers (10um):	0.354
Human Hepatotoxicity (H-HT):	0.32	Drug-induced Liver Injury (DILI):	0.007
AMES Toxicity:	0.029	Rat Oral Acute Toxicity:	0.018
Maximum Recommended Daily Dose:	0.128	Skin Sensitization:	0.99
Carcinogencity:	0.054	Eye Corrosion:	0.977
Eye Irritation:	0.995	Respiratory Toxicity:	0.851
Drug-induced Neurotoxicity:	0.005	Ototoxicity:	0.757
Hematotoxicity:	0.081	Drug-induced Nephrotoxicity:	0.553
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.057	Hek293 Cytotoxicity:	0.027
BCF:	1.117 ? 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:	4.027 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.368 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.761 ? 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
NPO30941	Holarrhena antidysenterica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30941	Holarrhena antidysenterica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30941	Holarrhena antidysenterica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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 NPC317999 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	26570
0.1-0.2	20758
0.2-0.3	2034
0.3-0.4	315
0.4-0.5	94
0.5-0.6	50
0.6-0.7	14
0.7-0.8	2
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.825	Intermediate Similarity	NPC243532
0.8158	Intermediate Similarity	NPC606120
0.7778	Intermediate Similarity	NPC324004
0.7778	Intermediate Similarity	NPC328497
0.7381	Intermediate Similarity	NPC255863
0.7381	Intermediate Similarity	NPC136164
0.7381	Intermediate Similarity	NPC245947
0.7222	Intermediate Similarity	NPC424
0.7222	Intermediate Similarity	NPC36061
0.7222	Intermediate Similarity	NPC69510
0.7222	Intermediate Similarity	NPC77272
0.7222	Intermediate Similarity	NPC290563
0.7222	Intermediate Similarity	NPC139029
0.7222	Intermediate Similarity	NPC281972
0.7222	Intermediate Similarity	NPC261831
0.7222	Intermediate Similarity	NPC87564
0.6944	Remote Similarity	NPC281245
0.6757	Remote Similarity	NPC92114
0.6667	Remote Similarity	NPC154245
0.6667	Remote Similarity	NPC85813
0.6667	Remote Similarity	NPC223697
0.6667	Remote Similarity	NPC6095
0.6579	Remote Similarity	NPC95145
0.6579	Remote Similarity	NPC325642
0.6579	Remote Similarity	NPC65174
0.641	Remote Similarity	NPC321062
0.617	Remote Similarity	NPC323045
0.617	Remote Similarity	NPC49863
0.617	Remote Similarity	NPC317881
0.6	Remote Similarity	NPC5413
0.5957	Remote Similarity	NPC327112
0.587	Remote Similarity	NPC99619
0.5854	Remote Similarity	NPC52955
0.5854	Remote Similarity	NPC88966
0.5854	Remote Similarity	NPC25417
0.5854	Remote Similarity	NPC1813
0.5854	Remote Similarity	NPC59051
0.5778	Remote Similarity	NPC477201
0.5625	Remote Similarity	NPC470320
0.561	Remote Similarity	NPC91495
0.561	Remote Similarity	NPC70387
0.56	Remote Similarity	NPC605544
0.56	Remote Similarity	NPC607260
0.5556	Remote Similarity	NPC171736
0.5556	Remote Similarity	NPC301585
0.5556	Remote Similarity	NPC261080
0.5556	Remote Similarity	NPC132565
0.5556	Remote Similarity	NPC209970
0.5556	Remote Similarity	NPC216630
0.5556	Remote Similarity	NPC201844
0.5556	Remote Similarity	NPC301696
0.5556	Remote Similarity	NPC196924
0.5556	Remote Similarity	NPC307783
0.5556	Remote Similarity	NPC154186
0.5556	Remote Similarity	NPC149184
0.5556	Remote Similarity	NPC279026
0.5556	Remote Similarity	NPC113928
0.5556	Remote Similarity	NPC14227
0.5435	Remote Similarity	NPC106851
0.5435	Remote Similarity	NPC282788
0.5435	Remote Similarity	NPC274927
0.5417	Remote Similarity	NPC68343
0.5417	Remote Similarity	NPC321838
0.5417	Remote Similarity	NPC318420
0.5417	Remote Similarity	NPC325627
0.5417	Remote Similarity	NPC323477
0.5417	Remote Similarity	NPC326268
0.5417	Remote Similarity	NPC328089
0.5333	Remote Similarity	NPC225929
0.5319	Remote Similarity	NPC179764
0.5283	Remote Similarity	NPC319007
0.5278	Remote Similarity	NPC155263
0.5208	Remote Similarity	NPC251042
0.5208	Remote Similarity	NPC473863
0.5208	Remote Similarity	NPC174447
0.5208	Remote Similarity	NPC122521
0.52	Remote Similarity	NPC26500
0.5128	Remote Similarity	NPC180534
0.5128	Remote Similarity	NPC611531
0.5091	Remote Similarity	NPC227396

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC317999 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6210
0.1-0.2	2675
0.2-0.3	215
0.3-0.4	20
0.4-0.5	16
0.5-0.6	7
0.6-0.7	4
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
0.7222	Intermediate Similarity	NPD3195	Phase 2
0.7222	Intermediate Similarity	NPD3196	Approved
0.6829	Remote Similarity	NPD3194	Phase 4
0.6667	Remote Similarity	NPD4266	Phase 2
0.617	Remote Similarity	NPD4247	Clinical (unspecified phase)
0.6	Remote Similarity	NPD3173	Phase 4
0.5957	Remote Similarity	NPD4246	Phase 2
0.5854	Remote Similarity	NPD3172	Approved
0.5556	Remote Similarity	NPD2270	Pre-clinical
0.5556	Remote Similarity	NPD633	Phase 3
0.5556	Remote Similarity	NPD9448	Phase 2
0.5417	Remote Similarity	NPD39	Phase 4
0.5128	Remote Similarity	NPD622	Pre-clinical

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