NPASS Compound

Natural Product: NPC594036

Natural Product ID	NPC594036
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Hemirepanduline
IUPAC Name	6-methoxy-1-[(4-methoxyphenyl)methyl]-2,8-dimethyl-3,4-dihydro-1~{H}-isoquinolin-7-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 49 51 0 0 0 0 0 0 0 0999 V2000 6.9183 1.5302 -0.1733 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2024 0.4582 -0.7360 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9052 0.1325 -0.3254 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2590 -0.9379 -0.9241 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9753 -1.2194 -0.4818 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3461 -0.5094 0.4850 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9338 -0.8128 0.9688 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0342 -0.0520 0.1885 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4686 -0.1426 0.4352 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1146 -1.1062 1.1666 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4233 -2.2375 1.8254 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5055 -0.9776 1.2553 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1860 -1.9403 1.9909 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2008 0.0467 0.6517 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5812 0.1056 0.7862 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2794 1.1630 0.1605 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5320 1.0042 -0.0792 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1888 0.9019 -0.1795 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3393 1.8711 -0.9512 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4417 1.0626 -1.8408 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1084 -0.1283 -1.2525 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.4608 -1.2865 -1.8363 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9979 0.5483 1.0696 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2966 0.8777 0.6615 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7965 1.7093 -0.8470 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2748 1.2594 0.8506 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3174 2.4478 -0.1085 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7300 -1.5184 -1.6913 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4528 -2.0525 -0.9373 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9056 -1.9245 0.8810 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9439 -0.4445 2.0145 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2430 1.0511 0.3856 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2349 -2.7706 2.4228 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1037 -3.0312 1.1201 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6992 -1.9603 2.5976 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3692 -2.8398 1.5420 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3011 1.1681 0.5894 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8272 2.1583 0.3796 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2817 0.9526 -0.9283 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0437 1.8261 -0.5696 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0394 2.4234 -1.6461 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8444 2.6094 -0.3227 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3962 1.7243 -2.2026 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9863 0.7715 -2.7593 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5445 -1.0630 -2.0625 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4184 -2.1972 -1.2227 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0202 -1.5212 -2.8083 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5791 1.1716 1.8464 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8473 1.6989 1.0913 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 1 0 8 9 1 0 9 10 2 0 10 11 1 0 10 12 1 0 12 13 1 0 12 14 2 0 14 15 1 0 15 16 1 0 14 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 6 23 1 0 23 24 2 0 24 3 1 0 21 8 1 0 18 9 1 0 1 25 1 0 1 26 1 0 1 27 1 0 4 28 1 0 5 29 1 0 7 30 1 0 7 31 1 0 8 32 1 0 11 33 1 0 11 34 1 0 11 35 1 0 13 36 1 0 16 37 1 0 16 38 1 0 16 39 1 0 17 40 1 0 19 41 1 0 19 42 1 0 20 43 1 0 20 44 1 0 22 45 1 0 22 46 1 0 22 47 1 0 23 48 1 0 24 49 1 0 M END

Standard InCHIKey	KLVDJUCERSCQAG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H25NO3/c1-13-19-15(12-18(24-4)20(13)22)9-10-21(2)17(19)11-14-5-7-16(23-3)8-6-14/h5-8,12,17,22H,9-11H2,1-4H3
SMILES	COC1=CC=C(CC2C3=C(C)C(O)=C(OC)C=C3CCN2C)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	327.18	Volume:	350.355 ? Van der Waals volume.
Dense:	0.934	LogP:	2.54 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.585 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.917 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	17.0
TPSA:	41.93 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.933	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.793	Fsp³:	0.4
MCE-18:	57.857 ? 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:	0.473	Fluc inhibitor:	0.018 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.379 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.325 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.005	Promiscuous compounds:	0.203

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.013	MDCK Permeability:	-4.779
Pgp-inhibitor:	0.948	Pgp-substrate:	0.03
PAMPA:	0.005 ? 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):	0.106
20% Bioavailability (F20%):	0.246	30% Bioavailability (F30%):	0.1
50% Bioavailability (F50%):	0.816

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.461	MRP1:	0.923
Plasma Protein Binding (PPB):	61.085%	Volume Distribution (VD):	0.02
Fu:	39.705% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.95	BCRP inhibitor:	0.787
BSEP inhibitor:	0.989

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.168
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.077
CYP2C9-inhibitor:	0.983	CYP2C9-substrate:	0.557
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.951
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.466
CYP2B6-substrate:	0.849	CYP2C8-inhibitor:	0.952
HLM stability:	0.955 ? 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):

10.162

Half-life (T1/2):

1.732

ADMET: Toxicity

hERG Blockers:	0.394	hERG Blockers (10um):	0.705
Human Hepatotoxicity (H-HT):	0.439	Drug-induced Liver Injury (DILI):	0.041
AMES Toxicity:	0.571	Rat Oral Acute Toxicity:	0.322
Maximum Recommended Daily Dose:	0.801	Skin Sensitization:	0.419
Carcinogencity:	0.679	Eye Corrosion:	0.0
Eye Irritation:	0.285	Respiratory Toxicity:	0.901
Drug-induced Neurotoxicity:	0.719	Ototoxicity:	0.694
Hematotoxicity:	0.131	Drug-induced Nephrotoxicity:	0.194
Genotoxicity:	0.345	RPMI-8226 Immunitoxicity:	0.073
A549 Cytotoxicity:	0.227	Hek293 Cytotoxicity:	0.574
BCF:	1.393 ? 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:	3.968 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.393 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.708 ? 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
NPO61333	Daphnandra	Genus	Atherospermataceae	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 NPC594036 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	26381
0.1-0.2	20317
0.2-0.3	2819
0.3-0.4	220
0.4-0.5	96
0.5-0.6	21
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	Natural Product ID
0.6909	Remote Similarity	NPC609731
0.6296	Remote Similarity	NPC314682
0.5932	Remote Similarity	NPC147390
0.5932	Remote Similarity	NPC428
0.5833	Remote Similarity	NPC135538
0.5833	Remote Similarity	NPC24233
0.5806	Remote Similarity	NPC104196
0.5667	Remote Similarity	NPC103379
0.5593	Remote Similarity	NPC185838
0.5574	Remote Similarity	NPC321505
0.5574	Remote Similarity	NPC179825
0.541	Remote Similarity	NPC191376
0.5362	Remote Similarity	NPC256012
0.5362	Remote Similarity	NPC610965
0.5345	Remote Similarity	NPC213206
0.5345	Remote Similarity	NPC188163
0.5345	Remote Similarity	NPC328750
0.5147	Remote Similarity	NPC317272
0.5147	Remote Similarity	NPC268503
0.5139	Remote Similarity	NPC603603
0.5068	Remote Similarity	NPC240841
0.5063	Remote Similarity	NPC601489
0.5063	Remote Similarity	NPC604804

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC594036 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3592
0.1-0.2	5186
0.2-0.3	356
0.3-0.4	12
0.4-0.5	3
0.5-0.6	1
0.6-0.7	0
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
0.5345	Remote Similarity	NPD4664	Clinical (unspecified phase)

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