NPASS Compound

Natural Product: NPC93989

Natural Product ID	NPC93989
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ROAHDZJDHGLGBA-QGZVFWFLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	9864120
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0000054] Benzylisoquinolines

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 53 0 0 0 0 0 0 0 0999 V2000 0.7200 -2.5574 0.3161 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9465 -1.3506 0.9996 N 0 0 0 0 0 0 0 0 0 0 0 0 2.1056 -1.4992 1.8602 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2916 -1.6603 0.8899 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4549 -0.2955 0.3062 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6758 0.2752 0.0389 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7989 1.5535 -0.4916 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6692 2.2913 -0.7665 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4405 1.7213 -0.4995 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3191 0.4371 0.0330 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9502 -0.1310 0.2972 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1506 -0.0337 -0.9435 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3058 -0.2587 -0.7981 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9183 -1.4324 -1.2036 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2755 -1.6334 -1.0761 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0903 -0.6643 -0.5339 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5190 0.5096 -0.1223 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1446 0.6950 -0.2591 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6357 1.9800 0.2052 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5564 2.9652 -0.5665 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3223 1.5164 0.4341 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4759 1.4360 1.8548 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4676 -0.8529 -0.3978 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0810 -2.0542 -0.8144 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0743 3.5299 -1.2879 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4507 3.7218 -0.9430 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8721 2.3584 -0.8520 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8567 -2.5388 -0.7719 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4099 -3.3478 0.6957 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2943 -2.9446 0.6322 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3314 -0.5510 2.4207 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0278 -2.3523 2.5457 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1516 -1.9615 1.5010 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1236 -2.4252 0.1359 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5500 -0.3032 0.2547 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5896 2.3454 -0.7280 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5045 0.6311 1.0128 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2667 1.0008 -1.3598 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5088 -0.6865 -1.7710 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3509 -2.2419 -1.6455 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7414 -2.5689 -1.4026 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3206 2.0974 1.2260 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3090 2.0406 2.2078 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4868 1.7186 2.2785 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6338 0.3688 2.1716 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5169 -2.9631 -0.4866 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1750 -2.1310 -1.9206 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0939 -2.1666 -0.4014 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4831 4.1281 0.0752 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9914 4.2847 -1.6994 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 17 21 1 0 21 22 1 0 16 23 1 0 23 24 1 0 8 25 1 0 25 26 1 0 26 27 1 0 11 2 1 0 18 13 1 0 10 5 1 0 27 7 1 0 1 28 1 0 1 29 1 0 1 30 1 0 3 31 1 0 3 32 1 0 4 33 1 0 4 34 1 0 6 35 1 0 9 36 1 0 11 37 1 1 12 38 1 0 12 39 1 0 14 40 1 0 15 41 1 0 19 42 1 0 22 43 1 0 22 44 1 0 22 45 1 0 24 46 1 0 24 47 1 0 24 48 1 0 26 49 1 0 26 50 1 0 M END

Standard InCHIKey	ROAHDZJDHGLGBA-QGZVFWFLSA-N
Standard InCHI	InChI=1S/C21H23NO5/c1-22-7-6-14-9-19-20(27-12-26-19)10-15(14)17(22)8-13-4-5-18(24-2)21(25-3)16(13)11-23/h4-5,9-11,17H,6-8,12H2,1-3H3/t17-/m1/s1
SMILES	CN1CCc2cc3c(cc2[C@H]1Cc1ccc(c(c1C=O)OC)OC)OCO3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	369.16	Volume:	374.039 ? Van der Waals volume.
Dense:	0.987	LogP:	2.32 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.348 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.312 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	22.0
TPSA:	57.23 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.755	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.174	Fsp³:	0.381
MCE-18:	72.069 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.47	Fluc inhibitor:	0.328 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.372 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.343 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.003	Promiscuous compounds:	0.614

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.885	MDCK Permeability:	-4.789
Pgp-inhibitor:	0.903	Pgp-substrate:	0.076
PAMPA:	0.002 ? 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%):	0.358	30% Bioavailability (F30%):	0.017
50% Bioavailability (F50%):	0.843

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.995	MRP1:	0.948
Plasma Protein Binding (PPB):	69.731%	Volume Distribution (VD):	0.224
Fu:	32.952% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.193
OATP1B3 inhibitor:	0.446	BCRP inhibitor:	0.237
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.304
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.996	CYP2C9-substrate:	0.492
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.977
CYP3A4-inhibitor:	0.666	CYP3A4-substrate:	0.926
CYP2B6-substrate:	0.989	CYP2C8-inhibitor:	0.0
HLM stability:	0.04 ? 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):

6.373

Half-life (T1/2):

2.138

ADMET: Toxicity

hERG Blockers:	0.483	hERG Blockers (10um):	0.605
Human Hepatotoxicity (H-HT):	0.592	Drug-induced Liver Injury (DILI):	0.134
AMES Toxicity:	0.615	Rat Oral Acute Toxicity:	0.644
Maximum Recommended Daily Dose:	0.905	Skin Sensitization:	0.269
Carcinogencity:	0.788	Eye Corrosion:	0.006
Eye Irritation:	0.356	Respiratory Toxicity:	0.881
Drug-induced Neurotoxicity:	0.936	Ototoxicity:	0.239
Hematotoxicity:	0.127	Drug-induced Nephrotoxicity:	0.478
Genotoxicity:	0.887	RPMI-8226 Immunitoxicity:	0.094
A549 Cytotoxicity:	0.133	Hek293 Cytotoxicity:	0.298
BCF:	1.568 ? 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:	4.041 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.806 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.984 ? 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
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	Roots; Rhizomes	n.a.	n.a.	PMID[15568768]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21661731]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22029392]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22029392]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29091439]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	roots	n.a.	n.a.	PMID[9784149]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2020	Corydalis cava	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1074	Hydrastis canadensis	Species	Ranunculaceae	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 NPC93989 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	35185
0.1-0.2	13193
0.2-0.3	1152
0.3-0.4	181
0.4-0.5	106
0.5-0.6	32
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC27887
0.6452	Remote Similarity	NPC216459
0.6452	Remote Similarity	NPC41178
0.6452	Remote Similarity	NPC138487
0.6034	Remote Similarity	NPC213206
0.6034	Remote Similarity	NPC188163
0.6034	Remote Similarity	NPC328750
0.5862	Remote Similarity	NPC314682
0.5846	Remote Similarity	NPC326205
0.5781	Remote Similarity	NPC31311
0.5781	Remote Similarity	NPC234392
0.5735	Remote Similarity	NPC226708
0.5507	Remote Similarity	NPC14622
0.5507	Remote Similarity	NPC70290
0.5507	Remote Similarity	NPC215098
0.5507	Remote Similarity	NPC124302
0.5507	Remote Similarity	NPC73020
0.5455	Remote Similarity	NPC475959
0.5397	Remote Similarity	NPC210437
0.5397	Remote Similarity	NPC16107
0.5397	Remote Similarity	NPC106295
0.5362	Remote Similarity	NPC276944
0.5362	Remote Similarity	NPC238530
0.5312	Remote Similarity	NPC51957
0.5294	Remote Similarity	NPC247389
0.5238	Remote Similarity	NPC185838
0.5231	Remote Similarity	NPC135538
0.5231	Remote Similarity	NPC24233
0.5224	Remote Similarity	NPC247639
0.5224	Remote Similarity	NPC25084
0.5143	Remote Similarity	NPC476432
0.5143	Remote Similarity	NPC24264
0.5091	Remote Similarity	NPC233029
0.5091	Remote Similarity	NPC210148
0.507	Remote Similarity	NPC481429
0.507	Remote Similarity	NPC481428
0.507	Remote Similarity	NPC481449
0.5065	Remote Similarity	NPC73492
0.5065	Remote Similarity	NPC299990

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC93989 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5035
0.1-0.2	3908
0.2-0.3	185
0.3-0.4	12
0.4-0.5	7
0.5-0.6	2
0.6-0.7	1
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
0.6034	Remote Similarity	NPD4664	Clinical (unspecified phase)
0.5507	Remote Similarity	NPD4420	Pre-clinical
0.5397	Remote Similarity	NPD4584	Phase 2

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