NPASS Compound

Natural Product: NPC541477

Natural Product ID	NPC541477
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Pakistanine
IUPAC Name	(6~{a}~{R})-9-[4-[[(1~{S})-6,7-dimethoxy-2-methyl-3,4-dihydro-1~{H}-isoquinolin-1-yl]methyl]phenoxy]-2-methoxy-6-methyl-5,6,6~{a},7-tetrahydro-4~{H}-dibenzo[de,g]quinoline-1,10-diol
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 85 91 0 0 0 0 0 0 0 0999 V2000 -8.1123 -2.3666 -2.9687 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2302 -1.2876 -2.9148 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7972 -0.8080 -1.6915 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2058 -1.3590 -0.4915 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7658 -0.8706 0.7257 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8935 0.1975 0.7584 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4962 0.7350 -0.4483 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9266 0.2586 -1.6744 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5005 0.8313 -2.8804 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6050 1.9256 -2.8003 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4522 0.6831 2.0751 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2284 -0.0346 2.5956 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1359 0.1882 1.6124 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2629 1.2485 1.6718 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2640 1.4285 0.7510 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0999 0.5349 -0.2838 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0987 0.6893 -1.2340 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2202 0.2907 -1.0511 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2018 1.2715 -1.1327 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5569 0.9914 -0.9666 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9133 -0.3187 -0.7140 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9749 -1.3040 -0.6271 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6256 -0.9897 -0.7973 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6904 -1.9887 -0.7074 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3385 -0.6465 -0.6060 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7364 -1.9157 -0.2555 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8875 -2.9752 -0.0706 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0830 -2.2036 -0.0608 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4931 -3.4976 0.2964 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8743 -3.7208 0.4781 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9905 -1.2011 -0.2251 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6100 0.1002 -0.5830 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2624 0.3742 -0.7767 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9033 1.7512 -1.2336 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5095 2.1243 -1.0169 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8307 2.6270 -0.5224 N 0 0 0 0 0 0 0 0 0 0 0 0 6.3964 4.0098 -0.5592 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1568 2.4594 -1.0630 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6880 1.1136 -0.7208 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9625 -0.5334 -0.3631 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9641 -0.7026 0.5714 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5366 0.7100 2.9822 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.2504 1.3657 4.2362 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3381 -0.4413 3.0894 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2006 -1.4580 2.0181 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5897 -3.2711 -2.6284 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9510 -2.1806 -2.2549 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5802 -2.4837 -3.9683 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8867 -2.1939 -0.4945 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8150 1.5697 -0.4335 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0087 2.7124 -2.1197 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6879 1.5326 -2.2713 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2902 2.2947 -3.7747 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1184 1.7530 1.9176 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9919 0.3675 3.5823 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3697 -1.1244 2.6832 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4131 1.9432 2.5013 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5896 2.2802 0.8279 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9087 2.3040 -1.3345 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1781 -2.3103 -0.4429 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7582 -2.7776 -0.0927 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1423 -3.9240 -0.3269 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0619 -4.7760 0.7553 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2804 -3.0005 1.2208 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4495 -3.5519 -0.4670 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0569 -1.3966 -0.0776 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2030 1.7555 -2.3326 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4281 2.6199 -0.0032 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1519 2.8528 -1.7835 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7763 4.2346 -1.4454 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2875 4.6695 -0.5555 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8641 4.2029 0.3945 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1957 2.6475 -2.1574 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8044 3.2499 -0.6141 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1754 1.2254 0.2984 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4466 0.7427 -1.4527 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8546 -1.2560 -1.1913 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6455 -1.5634 0.4930 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5913 0.7960 4.8935 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8693 2.3780 4.0690 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2323 1.4808 4.7711 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1609 -0.9378 4.0796 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4148 -0.1132 3.1402 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5276 -2.3165 2.3145 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1961 -1.9463 1.8590 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 26 28 1 0 28 29 1 0 29 30 1 0 28 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 36 38 1 0 38 39 1 0 16 40 1 0 40 41 2 0 11 42 1 0 42 43 1 0 42 44 1 0 44 45 1 0 8 3 1 0 41 13 1 0 45 5 1 0 23 18 1 0 33 25 1 0 35 20 1 0 39 32 1 0 1 46 1 0 1 47 1 0 1 48 1 0 4 49 1 0 7 50 1 0 10 51 1 0 10 52 1 0 10 53 1 0 11 54 1 6 12 55 1 0 12 56 1 0 14 57 1 0 15 58 1 0 19 59 1 0 22 60 1 0 24 61 1 0 27 62 1 0 30 63 1 0 30 64 1 0 30 65 1 0 31 66 1 0 34 67 1 6 35 68 1 0 35 69 1 0 37 70 1 0 37 71 1 0 37 72 1 0 38 73 1 0 38 74 1 0 39 75 1 0 39 76 1 0 40 77 1 0 41 78 1 0 43 79 1 0 43 80 1 0 43 81 1 0 44 82 1 0 44 83 1 0 45 84 1 0 45 85 1 0 M END

Standard InCHIKey	PJBCPYBIOOFQBE-URLMMPGGSA-N
Standard InCHI	InChI=1S/C37H40N2O6/c1-38-12-10-22-16-32(42-3)33(43-4)20-26(22)28(38)14-21-6-8-25(9-7-21)45-31-18-24-15-29-35-23(11-13-39(29)2)17-34(44-5)37(41)36(35)27(24)19-30(31)40/h6-9,16-20,28-29,40-41H,10-15H2,1-5H3/t28-,29+/m0/s1
SMILES	COC1=CC2=C(C=C1OC)[C@H](CC1=CC=C(OC3=CC4=C(C=C3O)C3=C(O)C(OC)=CC5=C3[C@@H](C4)N(C)CC5)C=C1)N(C)CC2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	608.29	Volume:	631.71 ? Van der Waals volume.
Dense:	0.963	LogP:	2.909 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.699 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.814 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	37.0
TPSA:	83.86 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	2.0	Rings:	7.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.248	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.809	Fsp³:	0.351
MCE-18:	131.2 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.995	Fluc inhibitor:	0.011 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.728 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.951 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.268

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.175	MDCK Permeability:	-4.818
Pgp-inhibitor:	0.464	Pgp-substrate:	0.358
PAMPA:	0.001 ? 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):	0.003
20% Bioavailability (F20%):	0.941	30% Bioavailability (F30%):	0.729
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.075	MRP1:	0.987
Plasma Protein Binding (PPB):	79.928%	Volume Distribution (VD):	-0.028
Fu:	24.065% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.989	BCRP inhibitor:	0.855
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.466
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.672
CYP2B6-substrate:	0.991	CYP2C8-inhibitor:	0.441
HLM stability:	0.688 ? 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):

5.526

Half-life (T1/2):

3.155

ADMET: Toxicity

hERG Blockers:	0.854	hERG Blockers (10um):	0.794
Human Hepatotoxicity (H-HT):	0.844	Drug-induced Liver Injury (DILI):	0.02
AMES Toxicity:	0.814	Rat Oral Acute Toxicity:	0.811
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	0.383
Carcinogencity:	0.561	Eye Corrosion:	0.0
Eye Irritation:	0.008	Respiratory Toxicity:	0.964
Drug-induced Neurotoxicity:	0.939	Ototoxicity:	0.729
Hematotoxicity:	0.028	Drug-induced Nephrotoxicity:	0.391
Genotoxicity:	0.994	RPMI-8226 Immunitoxicity:	0.085
A549 Cytotoxicity:	0.409	Hek293 Cytotoxicity:	0.789
BCF:	1.711 ? 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:	4.893 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.168 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.613 ? 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]
NPO6161	Berberis baluchistanica	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6204	Berberis empetrifolia	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO42933	Berberis waziristanica	Genus	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6161	Berberis baluchistanica	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6204	Berberis empetrifolia	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6161	Berberis baluchistanica	Species	Berberidaceae	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 NPC541477 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	29741
0.1-0.2	18749
0.2-0.3	1094
0.3-0.4	114
0.4-0.5	98
0.5-0.6	52
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
0.6494	Remote Similarity	NPC317272
0.6494	Remote Similarity	NPC268503
0.6486	Remote Similarity	NPC606254
0.6341	Remote Similarity	NPC240841
0.6024	Remote Similarity	NPC603603
0.5682	Remote Similarity	NPC112248
0.5658	Remote Similarity	NPC135538
0.5658	Remote Similarity	NPC24233
0.5641	Remote Similarity	NPC247639
0.5641	Remote Similarity	NPC212794
0.5641	Remote Similarity	NPC25084
0.5584	Remote Similarity	NPC158376
0.557	Remote Similarity	NPC117188
0.557	Remote Similarity	NPC145832
0.5568	Remote Similarity	NPC609914
0.5495	Remote Similarity	NPC181796
0.5495	Remote Similarity	NPC54654
0.5495	Remote Similarity	NPC7715
0.5495	Remote Similarity	NPC328155
0.5495	Remote Similarity	NPC222661
0.5495	Remote Similarity	NPC285931
0.5488	Remote Similarity	NPC199465
0.5476	Remote Similarity	NPC256012
0.5476	Remote Similarity	NPC610965
0.5443	Remote Similarity	NPC609009
0.5375	Remote Similarity	NPC605949
0.5342	Remote Similarity	NPC314682
0.5326	Remote Similarity	NPC290005
0.5309	Remote Similarity	NPC205421
0.5309	Remote Similarity	NPC607722
0.5281	Remote Similarity	NPC290582
0.5281	Remote Similarity	NPC217748
0.5281	Remote Similarity	NPC182052
0.5281	Remote Similarity	NPC271013
0.5281	Remote Similarity	NPC42663
0.5281	Remote Similarity	NPC15414
0.5275	Remote Similarity	NPC185639
0.5275	Remote Similarity	NPC251735
0.5275	Remote Similarity	NPC49075
0.5275	Remote Similarity	NPC599951
0.5269	Remote Similarity	NPC302275
0.5263	Remote Similarity	NPC185838
0.5222	Remote Similarity	NPC279228
0.5217	Remote Similarity	NPC274716
0.5217	Remote Similarity	NPC167116
0.5217	Remote Similarity	NPC609821
0.5208	Remote Similarity	NPC478963
0.5165	Remote Similarity	NPC311973
0.5165	Remote Similarity	NPC286119
0.5165	Remote Similarity	NPC239824
0.5109	Remote Similarity	NPC223690
0.5109	Remote Similarity	NPC9532
0.5067	Remote Similarity	NPC213206
0.5067	Remote Similarity	NPC188163
0.5067	Remote Similarity	NPC328750
0.5062	Remote Similarity	NPC104196
0.5053	Remote Similarity	NPC212237

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC541477 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5032
0.1-0.2	4043
0.2-0.3	63
0.3-0.4	5
0.4-0.5	6
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
0.5067	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