NPASS Compound

Natural Product: NPC79378

Natural Product ID	NPC79378
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LMGZCSKYOKDBES-SJLPKXTDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	70897566
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002188] Phthalide isoquinolines

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 50 54 0 0 0 0 0 0 0 0999 V2000 -1.7176 -2.9492 -2.1742 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0876 -1.6806 -1.6728 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5761 -0.7484 -2.6442 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1702 0.4844 -2.0317 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9257 0.5526 -0.5632 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7004 1.3782 0.2186 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5036 1.4534 1.5821 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5245 0.7024 2.1970 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7202 -0.1448 1.4377 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9504 -0.1880 0.0868 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1257 -1.0839 -0.7622 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1487 -0.1949 -1.5446 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9447 0.3236 -0.7074 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0536 1.2389 0.3177 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2794 1.4922 0.9470 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4228 0.8296 0.5574 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3298 -0.0863 -0.4662 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1163 -0.3349 -1.0878 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8116 -1.2153 -2.2089 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6641 -1.9612 -2.7904 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4863 -1.0760 -2.4871 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4810 -0.7538 -0.8593 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7515 -1.9871 -0.1792 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6594 1.0460 1.1510 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7167 1.9961 2.2013 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7310 -0.9027 2.0621 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5734 0.9904 3.5441 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1565 2.2731 3.6614 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1287 2.1919 2.6067 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9118 -3.4378 -1.5766 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6034 -3.6380 -2.0815 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4569 -2.9354 -3.2513 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7990 -0.4274 -3.3716 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3384 -1.2772 -3.2534 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8571 1.4264 -2.5454 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2965 0.3962 -2.1270 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4782 1.9760 -0.2630 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6094 -1.8790 -0.2292 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6691 0.6228 -2.0459 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1835 1.8004 0.6586 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3337 2.2159 1.7489 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2645 -1.7173 0.7860 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4296 -2.6341 -0.7519 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8035 -2.4834 0.1204 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9505 1.6792 2.9442 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4197 3.0214 1.8392 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7227 2.0617 2.6401 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0168 -1.8580 2.3263 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6423 2.4255 4.6432 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4057 3.0166 3.3979 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 17 22 1 0 22 23 1 0 16 24 1 0 24 25 1 0 9 26 1 0 8 27 1 0 27 28 1 0 28 29 1 0 11 2 1 0 21 12 1 0 10 5 1 0 18 13 1 0 29 7 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 6 37 1 0 11 38 1 1 12 39 1 6 14 40 1 0 15 41 1 0 23 42 1 0 23 43 1 0 23 44 1 0 25 45 1 0 25 46 1 0 25 47 1 0 26 48 1 0 28 49 1 0 28 50 1 0 M END

Standard InCHIKey	LMGZCSKYOKDBES-SJLPKXTDSA-N
Standard InCHI	InChI=1S/C21H21NO7/c1-22-7-6-10-8-13-20(28-9-27-13)17(23)14(10)16(22)18-11-4-5-12(25-2)19(26-3)15(11)21(24)29-18/h4-5,8,16,18,23H,6-7,9H2,1-3H3/t16-,18-/m1/s1
SMILES	CN1CCc2cc3c(c(c2[C@@H]1[C@H]1c2ccc(c(c2C(=O)O1)OC)OC)O)OCO3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	399.13	Volume:	383.063 ? Van der Waals volume.
Dense:	1.042	LogP:	1.508 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.755 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.969 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	26.0
TPSA:	86.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	8.0

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:	3.615	Fsp³:	0.381
MCE-18:	93.655 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.471	Fluc inhibitor:	0.413 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.617 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.486 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.003	Promiscuous compounds:	0.201

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.005	MDCK Permeability:	-4.767
Pgp-inhibitor:	0.987	Pgp-substrate:	0.043
PAMPA:	0.178 ? 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):	0.028
20% Bioavailability (F20%):	0.085	30% Bioavailability (F30%):	0.167
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.22	MRP1:	0.939
Plasma Protein Binding (PPB):	71.952%	Volume Distribution (VD):	0.035
Fu:	31.474% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.815
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.97	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.822	CYP2C19-substrate:	0.363
CYP2C9-inhibitor:	0.103	CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.877	CYP2D6-substrate:	0.984
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.07	CYP2C8-inhibitor:	0.008
HLM stability:	0.994 ? 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):

5.131

Half-life (T1/2):

1.993

ADMET: Toxicity

hERG Blockers:	0.126	hERG Blockers (10um):	0.628
Human Hepatotoxicity (H-HT):	0.385	Drug-induced Liver Injury (DILI):	0.287
AMES Toxicity:	0.529	Rat Oral Acute Toxicity:	0.202
Maximum Recommended Daily Dose:	0.661	Skin Sensitization:	0.769
Carcinogencity:	0.773	Eye Corrosion:	0.007
Eye Irritation:	0.819	Respiratory Toxicity:	0.212
Drug-induced Neurotoxicity:	0.574	Ototoxicity:	0.389
Hematotoxicity:	0.128	Drug-induced Nephrotoxicity:	0.377
Genotoxicity:	0.764	RPMI-8226 Immunitoxicity:	0.061
A549 Cytotoxicity:	0.038	Hek293 Cytotoxicity:	0.288
BCF:	1.417 ? 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:	3.972 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.141 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.98 ? 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
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1042/BA20020118]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1556/abot.45.2003.3-4.15]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15019787]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22029392]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23517479]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37685099]
NPO10176	Chrozophora prostrata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7312	Aplidium multiplicatum	Species	Polyclinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2466	Aloe microstigma	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	Latex Exudate	n.a.	n.a.	Database[FooDB]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10176	Chrozophora prostrata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2466	Aloe microstigma	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7312	Aplidium multiplicatum	Species	Polyclinidae	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 NPC79378 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	27856
0.1-0.2	19851
0.2-0.3	1955
0.3-0.4	173
0.4-0.5	10
0.5-0.6	0
0.6-0.7	5
0.7-0.8	3
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
0.7246	Intermediate Similarity	NPC14622
0.7246	Intermediate Similarity	NPC70290
0.7246	Intermediate Similarity	NPC215098
0.7246	Intermediate Similarity	NPC124302
0.7246	Intermediate Similarity	NPC73020
0.7042	Intermediate Similarity	NPC119818
0.7042	Intermediate Similarity	NPC328700
0.7042	Intermediate Similarity	NPC202771
0.7042	Intermediate Similarity	NPC2173
0.6667	Remote Similarity	NPC46744
0.6389	Remote Similarity	NPC120671
0.6389	Remote Similarity	NPC226652
0.6389	Remote Similarity	NPC219113
0.6389	Remote Similarity	NPC72788

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC79378 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4606
0.1-0.2	4395
0.2-0.3	141
0.3-0.4	4
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
0.7-0.8	3
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
0.7246	Intermediate Similarity	NPD4420	Pre-clinical
0.7042	Intermediate Similarity	NPD5005	Approved
0.7042	Intermediate Similarity	NPD5006	Phase 4

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