NPASS Compound

Natural Product: NPC537921

Natural Product ID	NPC537921
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-O-Methylpakistanine
IUPAC Name	(6~{a}~{R})-9-[4-[[(1~{S})-6,7-dimethoxy-2-methyl-3,4-dihydro-1~{H}-isoquinolin-1-yl]methyl]phenoxy]-1,2-dimethoxy-6-methyl-5,6,6~{a},7-tetrahydro-4~{H}-dibenzo[de,g]quinolin-10-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 88 94 0 0 0 0 0 0 0 0999 V2000 11.2456 0.4123 1.8266 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0704 1.0570 2.2444 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8714 0.7727 1.6409 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8112 -0.1490 0.6184 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5907 -0.4381 0.0041 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4511 0.1883 0.4108 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4857 1.1235 1.4419 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6970 1.3943 2.0339 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7919 2.3186 3.0675 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6314 2.9835 3.5112 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1451 -0.1001 -0.2245 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3949 -1.0586 0.6748 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0575 -1.4273 0.1686 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9441 -0.6431 0.4931 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7011 -0.9842 0.0299 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4703 -2.0875 -0.7619 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7809 -2.4311 -1.2296 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9504 -1.7651 -1.0580 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9866 -2.3851 -0.4059 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2107 -1.7288 -0.2095 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3599 -0.4283 -0.6917 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3269 0.1898 -1.3433 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1012 -0.4931 -1.5272 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0759 0.1780 -2.1964 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6677 0.2559 -0.6201 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8077 1.5428 -1.0535 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8446 2.3654 -1.5811 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1692 3.3263 -0.7287 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0667 2.1531 -0.9529 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2880 3.4531 -1.3761 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5715 4.0292 -1.2572 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1116 1.4482 -0.4220 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9717 0.1728 0.0125 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7359 -0.4488 -0.0808 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6056 -1.8394 0.3712 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2690 -2.4088 0.5230 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3473 -1.8849 1.6506 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.9306 -0.7798 2.4951 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7354 -1.7934 1.3292 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1239 -0.5785 0.5771 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5714 -2.8550 -1.0769 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8572 -2.5377 -0.6217 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3494 -0.5631 -1.5545 N 0 0 0 0 0 0 0 0 0 0 0 0 5.5752 0.5710 -2.4302 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2866 -1.6097 -1.7511 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5967 -1.4192 -1.0677 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2531 -0.6689 2.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 12.1417 0.9088 2.3002 H 0 0 0 0 0 0 0 0 0 0 0 0 11.4156 0.4690 0.7331 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7323 -0.6242 0.3241 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5705 1.5997 1.7388 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9503 3.8062 4.1986 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0844 3.4642 2.6507 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9451 2.3336 4.0560 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5763 0.8685 -0.3217 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3085 -0.6855 1.6967 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0021 -2.0008 0.7023 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1476 0.2239 1.1193 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1345 -0.3519 0.3075 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9271 -3.3882 -0.0144 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3744 1.1483 -1.7753 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8738 -0.1393 -3.1530 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1392 3.4898 -1.1064 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7192 4.2768 -0.8881 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1549 2.9812 0.3117 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9860 3.9404 -0.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6063 5.0780 -1.5477 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3115 3.4935 -1.9014 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0985 1.9054 -0.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2375 -2.4633 -0.3228 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0167 -2.4589 1.6366 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3054 -3.4778 0.1576 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4299 0.0288 1.9446 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8504 -0.3873 2.9861 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2567 -1.1244 3.2977 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3063 -1.8145 2.3048 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0181 -2.7466 0.8212 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7873 0.1121 1.1443 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7393 -0.8983 -0.3155 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3942 -3.7323 -1.7047 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6715 -3.1896 -0.9069 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8948 1.4759 -1.8535 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3080 0.3546 -3.2321 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6268 0.8651 -2.9668 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4417 -1.6827 -2.8734 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8827 -2.6229 -1.4947 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0306 -2.4098 -0.7531 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3382 -1.0549 -1.8403 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 2 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 21 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 26 29 1 0 29 30 1 0 30 31 1 0 29 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 1 0 35 37 1 0 37 38 1 0 37 39 1 0 39 40 1 0 16 41 1 0 41 42 2 0 11 43 1 0 43 44 1 0 43 45 1 0 45 46 1 0 8 3 1 0 42 13 1 0 46 5 1 0 23 18 1 0 34 25 1 0 36 20 1 0 40 33 1 0 1 47 1 0 1 48 1 0 1 49 1 0 4 50 1 0 7 51 1 0 10 52 1 0 10 53 1 0 10 54 1 0 11 55 1 6 12 56 1 0 12 57 1 0 14 58 1 0 15 59 1 0 19 60 1 0 22 61 1 0 24 62 1 0 28 63 1 0 28 64 1 0 28 65 1 0 31 66 1 0 31 67 1 0 31 68 1 0 32 69 1 0 35 70 1 6 36 71 1 0 36 72 1 0 38 73 1 0 38 74 1 0 38 75 1 0 39 76 1 0 39 77 1 0 40 78 1 0 40 79 1 0 41 80 1 0 42 81 1 0 44 82 1 0 44 83 1 0 44 84 1 0 45 85 1 0 45 86 1 0 46 87 1 0 46 88 1 0 M END

Standard InCHIKey	XMPDJTPBQGEPGK-XZWHSSHBSA-N
Standard InCHI	InChI=1S/C38H42N2O6/c1-39-13-11-23-17-33(42-3)34(43-4)21-27(23)29(39)15-22-7-9-26(10-8-22)46-32-19-25-16-30-36-24(12-14-40(30)2)18-35(44-5)38(45-6)37(36)28(25)20-31(32)41/h7-10,17-21,29-30,41H,11-16H2,1-6H3/t29-,30+/m0/s1
SMILES	COC1=CC2=C(C=C1OC)[C@H](CC1=CC=C(OC3=CC4=C(C=C3O)C3=C(OC)C(OC)=CC5=C3[C@@H](C4)N(C)CC5)C=C1)N(C)CC2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	622.3	Volume:	649.006 ? Van der Waals volume.
Dense:	0.959	LogP:	3.243 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.949 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.248 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	37.0
TPSA:	72.86 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	7.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.232	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.796	Fsp³:	0.368
MCE-18:	130.769 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.998	Fluc inhibitor:	0.007 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.713 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.918 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.273

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.88	MDCK Permeability:	-4.739
Pgp-inhibitor:	0.926	Pgp-substrate:	0.518
PAMPA:	0.0 ? 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):	0.002
20% Bioavailability (F20%):	0.897	30% Bioavailability (F30%):	0.346
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.345	MRP1:	0.973
Plasma Protein Binding (PPB):	77.471%	Volume Distribution (VD):	0.189
Fu:	23.55% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.981
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.191
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.325
CYP2B6-substrate:	0.988	CYP2C8-inhibitor:	0.247
HLM stability:	0.604 ? 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):

10.934

Half-life (T1/2):

2.649

ADMET: Toxicity

hERG Blockers:	0.897	hERG Blockers (10um):	0.824
Human Hepatotoxicity (H-HT):	0.83	Drug-induced Liver Injury (DILI):	0.014
AMES Toxicity:	0.766	Rat Oral Acute Toxicity:	0.81
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	0.285
Carcinogencity:	0.611	Eye Corrosion:	0.0
Eye Irritation:	0.004	Respiratory Toxicity:	0.948
Drug-induced Neurotoxicity:	0.963	Ototoxicity:	0.711
Hematotoxicity:	0.035	Drug-induced Nephrotoxicity:	0.373
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.075
A549 Cytotoxicity:	0.29	Hek293 Cytotoxicity:	0.759
BCF:	1.883 ? 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:	4.875 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.654 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.769 ? 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
NPO44607	Berberis aristata	Species	Berberidaceae	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 NPC537921 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	29164
0.1-0.2	19371
0.2-0.3	1041
0.3-0.4	113
0.4-0.5	105
0.5-0.6	57
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
0.679	Remote Similarity	NPC112248
0.6667	Remote Similarity	NPC317272
0.6667	Remote Similarity	NPC268503
0.618	Remote Similarity	NPC478963
0.6098	Remote Similarity	NPC240841
0.5789	Remote Similarity	NPC247639
0.5789	Remote Similarity	NPC25084
0.5783	Remote Similarity	NPC603603
0.573	Remote Similarity	NPC302275
0.5714	Remote Similarity	NPC136508
0.5698	Remote Similarity	NPC606311
0.5679	Remote Similarity	NPC128560
0.5676	Remote Similarity	NPC99659
0.5676	Remote Similarity	NPC325871
0.5641	Remote Similarity	NPC474931
0.5616	Remote Similarity	NPC185838
0.561	Remote Similarity	NPC256012
0.561	Remote Similarity	NPC610965
0.56	Remote Similarity	NPC135538
0.56	Remote Similarity	NPC24233
0.5493	Remote Similarity	NPC314682
0.5443	Remote Similarity	NPC205421
0.5443	Remote Similarity	NPC607722
0.5393	Remote Similarity	NPC185639
0.5393	Remote Similarity	NPC251735
0.5393	Remote Similarity	NPC49075
0.5393	Remote Similarity	NPC599951
0.5333	Remote Similarity	NPC274716
0.5333	Remote Similarity	NPC167116
0.5333	Remote Similarity	NPC609821
0.5325	Remote Similarity	NPC326316
0.5325	Remote Similarity	NPC81733
0.5275	Remote Similarity	NPC181796
0.5275	Remote Similarity	NPC54654
0.5275	Remote Similarity	NPC7715
0.5275	Remote Similarity	NPC328155
0.5275	Remote Similarity	NPC222661
0.5275	Remote Similarity	NPC285931
0.5269	Remote Similarity	NPC30182
0.5222	Remote Similarity	NPC223690
0.5222	Remote Similarity	NPC9532
0.5208	Remote Similarity	NPC473589
0.5205	Remote Similarity	NPC213206
0.5205	Remote Similarity	NPC188163
0.5205	Remote Similarity	NPC328750
0.5161	Remote Similarity	NPC212237
0.5125	Remote Similarity	NPC600388
0.5111	Remote Similarity	NPC311973
0.5111	Remote Similarity	NPC286119
0.5111	Remote Similarity	NPC239824
0.5111	Remote Similarity	NPC600054
0.5111	Remote Similarity	NPC601504
0.5109	Remote Similarity	NPC290005
0.5106	Remote Similarity	NPC24260
0.5106	Remote Similarity	NPC611658
0.5056	Remote Similarity	NPC290582
0.5056	Remote Similarity	NPC217748
0.5056	Remote Similarity	NPC182052
0.5056	Remote Similarity	NPC271013
0.5056	Remote Similarity	NPC42663
0.5056	Remote Similarity	NPC15414
0.5052	Remote Similarity	NPC169959

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC537921 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4864
0.1-0.2	4191
0.2-0.3	82
0.3-0.4	7
0.4-0.5	5
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
0.5205	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