NPASS Compound

Natural Product: NPC572321

Natural Product ID	NPC572321
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(13~{a}~{S})-2,3,9,10-tetramethoxy-6,8,13,13~{a}-tetrahydro-5~{H}-isoquinolino[3,2-a]isoquinolin-11-ol
IUPAC Name	(13~{a}~{S})-2,3,9,10-tetramethoxy-6,8,13,13~{a}-tetrahydro-5~{H}-isoquinolino[3,2-a]isoquinolin-11-ol
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 55 0 0 0 0 0 0 0 0999 V2000 6.1886 0.2736 -2.3684 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9263 -0.1871 -1.0567 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6083 -0.1770 -0.6211 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5741 0.2673 -1.4346 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2603 0.2825 -1.0141 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0177 -0.1665 0.2596 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0274 -0.6084 1.0753 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3555 -0.6264 0.6572 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3876 -1.0718 1.4743 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1449 -1.5359 2.7880 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6193 -0.1610 0.7375 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1417 -1.3843 0.3262 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5854 -1.0840 0.2535 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4403 -2.1205 -0.1086 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8030 -1.8599 -0.1834 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6451 -2.9197 -0.5502 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3282 -0.6203 0.0870 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6873 -0.3576 0.0131 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5794 -0.5015 1.0892 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4840 0.4042 0.4448 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9313 1.6836 0.7337 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0571 2.6822 -0.2418 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1347 0.1492 0.5196 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2322 1.2612 0.9065 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0298 1.0745 0.2660 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0681 1.1531 -1.1527 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1576 0.7631 -1.9002 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2685 0.3465 -2.5525 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7192 1.2983 -2.4386 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6604 -0.4207 -3.0557 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7819 0.6200 -2.4413 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8489 -0.9665 2.0859 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4733 -0.8466 3.3508 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1327 -1.4688 3.3262 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8255 -2.5844 2.8309 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5764 -0.1067 1.8618 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0144 -2.1580 1.1191 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2472 -1.8407 -0.6077 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0701 -3.1105 -0.3297 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2611 -2.7830 -1.3436 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5188 0.4088 1.7208 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3586 -1.4352 1.6756 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6220 -0.5993 0.6701 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6642 2.2936 -1.2029 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1428 2.9662 -0.3166 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5234 3.6143 -0.0012 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0620 1.1675 2.0109 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6778 2.2584 0.7322 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9060 0.4941 -1.5258 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4071 2.1896 -1.4057 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5265 1.6631 -2.4524 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9591 0.0026 -2.7105 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 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 6 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 18 19 1 0 17 20 1 0 20 21 1 0 21 22 1 0 20 23 2 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 8 3 1 0 25 11 1 0 27 5 1 0 23 13 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 7 32 1 0 10 33 1 0 10 34 1 0 10 35 1 0 11 36 1 1 12 37 1 0 12 38 1 0 14 39 1 0 16 40 1 0 19 41 1 0 19 42 1 0 19 43 1 0 22 44 1 0 22 45 1 0 22 46 1 0 24 47 1 0 24 48 1 0 26 49 1 0 26 50 1 0 27 51 1 0 27 52 1 0 M END

Standard InCHIKey	DKCQBFHZGAIJOJ-INIZCTEOSA-N
Standard InCHI	InChI=1S/C21H25NO5/c1-24-18-9-12-5-6-22-11-15-13(7-16(22)14(12)10-19(18)25-2)8-17(23)21(27-4)20(15)26-3/h8-10,16,23H,5-7,11H2,1-4H3/t16-/m0/s1
SMILES	COC1=CC2=C(C=C1OC)[C@@H]1CC3=CC(O)=C(OC)C(OC)=C3CN1CC2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	371.17	Volume:	376.675 ? Van der Waals volume.
Dense:	0.985	LogP:	1.501 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.838 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.239 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	21.0
TPSA:	60.39 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.891	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.052	Fsp³:	0.429
MCE-18:	76.667 ? 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:	0
Colloidal aggregators:	0.161	Fluc inhibitor:	0.044 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.55 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.534 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.118

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.903	MDCK Permeability:	-4.714
Pgp-inhibitor:	0.001	Pgp-substrate:	0.949
PAMPA:	0.018 ? 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):	0.007
20% Bioavailability (F20%):	0.345	30% Bioavailability (F30%):	0.508
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.185	MRP1:	0.994
Plasma Protein Binding (PPB):	83.21%	Volume Distribution (VD):	-0.067
Fu:	15.385% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.935
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.732
BSEP inhibitor:	0.845

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.01
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.963	CYP2C9-substrate:	0.925
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.025
CYP3A4-inhibitor:	0.975	CYP3A4-substrate:	0.851
CYP2B6-substrate:	0.218	CYP2C8-inhibitor:	0.914
HLM stability:	0.815 ? 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):

10.379

Half-life (T1/2):

1.936

ADMET: Toxicity

hERG Blockers:	0.426	hERG Blockers (10um):	0.66
Human Hepatotoxicity (H-HT):	0.525	Drug-induced Liver Injury (DILI):	0.098
AMES Toxicity:	0.412	Rat Oral Acute Toxicity:	0.713
Maximum Recommended Daily Dose:	0.755	Skin Sensitization:	0.72
Carcinogencity:	0.722	Eye Corrosion:	0.005
Eye Irritation:	0.292	Respiratory Toxicity:	0.938
Drug-induced Neurotoxicity:	0.803	Ototoxicity:	0.355
Hematotoxicity:	0.263	Drug-induced Nephrotoxicity:	0.415
Genotoxicity:	0.738	RPMI-8226 Immunitoxicity:	0.095
A549 Cytotoxicity:	0.237	Hek293 Cytotoxicity:	0.364
BCF:	1.816 ? 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:	3.95 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.288 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.432 ? 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
NPO62754	Stephania rotunda Lour.	Genus	Menispermaceae	Eukaryota	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 NPC572321 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	31019
0.1-0.2	17036
0.2-0.3	1563
0.3-0.4	170
0.4-0.5	30
0.5-0.6	12
0.6-0.7	27
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
0.7069	Intermediate Similarity	NPC39701
0.7069	Intermediate Similarity	NPC184026
0.6842	Remote Similarity	NPC210437
0.6842	Remote Similarity	NPC16107
0.6842	Remote Similarity	NPC106295
0.6724	Remote Similarity	NPC51957
0.6721	Remote Similarity	NPC204828
0.6721	Remote Similarity	NPC295691
0.6721	Remote Similarity	NPC207757
0.6721	Remote Similarity	NPC54379
0.6721	Remote Similarity	NPC5238
0.661	Remote Similarity	NPC151895
0.6452	Remote Similarity	NPC326205
0.6393	Remote Similarity	NPC276588
0.6393	Remote Similarity	NPC127674
0.6393	Remote Similarity	NPC278799
0.6364	Remote Similarity	NPC128019
0.6364	Remote Similarity	NPC232514
0.625	Remote Similarity	NPC606650
0.6129	Remote Similarity	NPC469817
0.6129	Remote Similarity	NPC189266
0.6129	Remote Similarity	NPC172765
0.6129	Remote Similarity	NPC2413
0.6129	Remote Similarity	NPC110416
0.6102	Remote Similarity	NPC88249
0.6102	Remote Similarity	NPC220858
0.6032	Remote Similarity	NPC216459
0.6032	Remote Similarity	NPC41178
0.6032	Remote Similarity	NPC138487
0.5873	Remote Similarity	NPC31311
0.5873	Remote Similarity	NPC234392
0.5846	Remote Similarity	NPC264850
0.5692	Remote Similarity	NPC312025
0.5672	Remote Similarity	NPC276944
0.5672	Remote Similarity	NPC238530
0.5538	Remote Similarity	NPC249797
0.5538	Remote Similarity	NPC193949
0.5397	Remote Similarity	NPC24465
0.5312	Remote Similarity	NPC135538
0.5312	Remote Similarity	NPC24233
0.5254	Remote Similarity	NPC34559

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC572321 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5611
0.1-0.2	3433
0.2-0.3	88
0.3-0.4	15
0.4-0.5	2
0.5-0.6	0
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
0.6842	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