NPASS Compound

Natural Product: NPC479995

Natural Product ID	NPC479995
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NEXWIAAPMUHYEP-GJZGRUSLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	10364043
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0002195] Naphthylisoquinolines

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 59 62 0 0 0 0 0 0 0 0999 V2000 2.3893 1.9278 2.8360 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6244 1.0805 1.6299 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6318 0.4142 0.9709 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8805 -0.3572 -0.1358 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8709 -1.0388 -0.8114 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1563 -1.8004 -1.9137 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4727 -1.8912 -2.3603 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4561 -1.2105 -1.6794 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1821 -0.4521 -0.5841 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2048 0.2045 0.0544 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9161 0.9747 1.1691 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4935 0.0870 -0.4215 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5779 0.7312 0.1852 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7587 -1.3095 -2.1335 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5123 -0.9083 -0.2948 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3278 0.0852 -0.7413 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7938 1.0459 -1.7680 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8590 1.6652 -2.5982 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7113 3.1897 -2.5592 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1918 1.3435 -2.2354 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.4165 1.3111 -0.8050 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8466 1.3262 -0.4263 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6127 0.2019 -0.2577 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1181 -0.6661 0.6816 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2890 -1.6724 1.1327 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9932 -1.7937 0.6477 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1694 -2.8140 1.1126 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6507 -3.7120 2.0655 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4282 -0.5418 1.1707 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8767 -1.4737 2.1367 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1834 1.6325 3.5693 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3973 1.7663 3.2620 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6047 2.9823 2.5705 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6209 0.5032 1.3398 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3641 -2.3303 -2.4373 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6756 -2.4986 -3.2333 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7387 1.4826 1.6554 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3597 1.7931 0.4437 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4652 0.7319 -0.4788 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8936 0.1581 1.0980 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4134 -1.9978 -1.7962 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1709 1.8295 -1.2814 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1063 0.4594 -2.4202 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7279 1.3997 -3.6854 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4305 3.5403 -1.5441 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8441 3.4352 -3.2213 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6573 3.6148 -2.9252 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5937 0.5154 -2.7030 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9488 2.2588 -0.4070 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4053 0.4237 -0.7072 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3286 2.1521 -1.0315 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9751 1.6533 0.6204 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6466 -2.3754 1.8701 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6331 -4.1382 1.7132 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9064 -3.1605 3.0001 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0010 -4.5808 2.2325 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6798 -2.5313 1.8180 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4827 -1.2610 3.1443 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9985 -1.4055 2.2184 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 8 14 1 0 5 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 24 29 1 0 29 30 1 0 11 2 1 0 26 15 1 0 9 4 1 0 23 16 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 6 35 1 0 7 36 1 0 11 37 1 0 13 38 1 0 13 39 1 0 13 40 1 0 14 41 1 0 17 42 1 0 17 43 1 0 18 44 1 6 19 45 1 0 19 46 1 0 19 47 1 0 20 48 1 0 21 49 1 1 22 50 1 0 22 51 1 0 22 52 1 0 25 53 1 0 28 54 1 0 28 55 1 0 28 56 1 0 30 57 1 0 30 58 1 0 30 59 1 0 M END

Standard InCHIKey	NEXWIAAPMUHYEP-GJZGRUSLSA-N
Standard InCHI	InChI=1S/C25H29NO4/c1-13-9-17-16(7-8-19(27)25(17)20(10-13)28-4)24-18-11-14(2)26-15(3)23(18)21(29-5)12-22(24)30-6/h7-10,12,14-15,26-27H,11H2,1-6H3/t14-,15-/m0/s1
SMILES	Cc1cc2c(ccc(c2c(c1)OC)O)c1c2C[C@H](C)N[C@@H](C)c2c(cc1OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	407.21	Volume:	431.796 ? Van der Waals volume.
Dense:	0.943	LogP:	3.826 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.287 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.776 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	22.0
TPSA:	59.95 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.627	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.574	Fsp³:	0.36
MCE-18:	79.412 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.875	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.395 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.425 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.165

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.146	MDCK Permeability:	-4.998
Pgp-inhibitor:	0.048	Pgp-substrate:	0.998
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%):	0.006	30% Bioavailability (F30%):	0.209
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.994
Plasma Protein Binding (PPB):	89.937%	Volume Distribution (VD):	0.73
Fu:	7.027% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.861	BCRP inhibitor:	0.095
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.94	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.788	CYP2C9-substrate:	0.949
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.83
CYP3A4-inhibitor:	0.807	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.479 ? 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):

6.95

Half-life (T1/2):

0.864

ADMET: Toxicity

hERG Blockers:	0.332	hERG Blockers (10um):	0.667
Human Hepatotoxicity (H-HT):	0.697	Drug-induced Liver Injury (DILI):	0.531
AMES Toxicity:	0.842	Rat Oral Acute Toxicity:	0.78
Maximum Recommended Daily Dose:	0.87	Skin Sensitization:	0.556
Carcinogencity:	0.593	Eye Corrosion:	0.0
Eye Irritation:	0.317	Respiratory Toxicity:	0.964
Drug-induced Neurotoxicity:	0.85	Ototoxicity:	0.645
Hematotoxicity:	0.506	Drug-induced Nephrotoxicity:	0.747
Genotoxicity:	0.87	RPMI-8226 Immunitoxicity:	0.158
A549 Cytotoxicity:	0.377	Hek293 Cytotoxicity:	0.558
BCF:	1.732 ? 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:	4.21 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.0 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.834 ? 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
NPO40017	Ancistrocladus ealaensis	Species	Ancistrocladaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11087584]
NPO40017	Ancistrocladus ealaensis	Species	Ancistrocladaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29560715]
NPO40017	Ancistrocladus ealaensis	Species	Ancistrocladaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31630523]
NPO40017	Ancistrocladus ealaensis	Species	Ancistrocladaceae	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

Activity Type	# Activity
IC50	11
MIC	2
Ratio IC50	2

Activity Type	# Activity
Cell line	2
Organism	10
Others	3

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
NPT839	Cell line	L6	Rattus norvegicus	MIC	=	90.0	ug.mL-1	PMID[11087584]
NPT839	Cell line	L6	Rattus norvegicus	IC50	=	77800.0	nM	PMID[29560715]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.79	ug.mL-1	PMID[11087584]
NPT844	Organism	Trypanosoma brucei rhodesiense	Trypanosoma brucei rhodesiense	IC50	=	2.03	ug.mL-1	PMID[11087584]
NPT844	Organism	Trypanosoma brucei rhodesiense	Trypanosoma brucei rhodesiense	IC50	=	3850.0	nM	PMID[29560715]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	760.0	nM	PMID[29560715]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	1740.0	nM	PMID[29560715]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	17.6	ug.mL-1	PMID[11087584]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	10.0	ug.mL-1	PMID[11087584]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	37900.0	nM	PMID[29560715]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	32500.0	nM	PMID[29560715]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	0.52	ug.mL-1	PMID[11087584]
NPT27	Others	Unspecified	n.a.	MIC	>	30.0	ug.mL-1	PMID[11087584]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	44.7	n.a.	PMID[29560715]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	102.0	n.a.	PMID[29560715]

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 NPC479995 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	26719
0.1-0.2	21208
0.2-0.3	1873
0.3-0.4	23
0.4-0.5	17
0.5-0.6	10
0.6-0.7	5
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
0.7031	Intermediate Similarity	NPC7393
0.6667	Remote Similarity	NPC480006
0.6522	Remote Similarity	NPC209377
0.6522	Remote Similarity	NPC479998
0.6	Remote Similarity	NPC479999
0.6	Remote Similarity	NPC480000
0.5753	Remote Similarity	NPC193853
0.5753	Remote Similarity	NPC223077
0.5443	Remote Similarity	NPC257269
0.5294	Remote Similarity	NPC479996
0.5294	Remote Similarity	NPC90773
0.527	Remote Similarity	NPC119068
0.527	Remote Similarity	NPC40496
0.5181	Remote Similarity	NPC480009
0.5132	Remote Similarity	NPC235143
0.5067	Remote Similarity	NPC480013

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479995 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4986
0.1-0.2	4117
0.2-0.3	46
0.3-0.4	0
0.4-0.5	0
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
0.527	Remote Similarity	NPD8453	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