NPASS Compound

Structure

NPC197743 OpenBabel07101719122D 84 85 0 0 1 0 0 0 0 0999 V2000 4.3301 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -7.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -7.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 -10.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -10.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -12.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -13.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -14.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 -14.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.1244 -12.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -13.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8157 -1.0248 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0827 1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5827 0.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1045 0.9945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -9.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -6.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -5.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -5.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -8.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3923 -11.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -12.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -13.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -5.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -2.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -6.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3301 -9.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5981 -7.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9135 -0.4067 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 -6.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4641 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -4.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.3923 -12.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1962 -12.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.7942 -12.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4641 -9.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -8.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -11.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1215 -1.3849 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 -12.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -12.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -5.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -7.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -8.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -10.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -5.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -12.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -4.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -6.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -6.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -9.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -9.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -10.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3783 -2.0540 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 -13.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -11.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0725 -1.6939 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -12.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 -12.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 17 1 0 0 0 0 2 31 1 0 0 0 0 3 31 1 0 0 0 0 4 32 1 0 0 0 0 5 32 1 0 0 0 0 6 33 1 0 0 0 0 7 33 1 0 0 0 0 8 34 1 0 0 0 0 9 34 1 0 0 0 0 10 35 1 0 0 0 0 11 35 1 0 0 0 0 13 66 1 0 0 0 0 14 66 1 0 0 0 0 15 67 1 0 0 0 0 16 82 1 0 0 0 0 18 19 2 0 0 0 0 18 20 1 0 0 0 0 19 22 1 0 0 0 0 20 23 2 0 0 0 0 21 24 1 0 0 0 0 21 25 1 0 0 0 0 22 37 2 0 0 0 0 23 37 1 0 0 0 0 24 42 1 0 0 0 0 25 68 1 0 0 0 0 26 31 1 0 0 0 0 27 32 1 0 0 0 0 28 37 1 0 0 0 0 29 45 1 0 0 0 0 30 44 1 0 0 0 0 30 46 1 0 0 0 0 36 12 1 6 0 0 0 36 47 1 0 0 0 0 36 69 1 0 0 0 0 38 17 1 6 0 0 0 38 55 1 0 0 0 0 38 61 1 0 0 0 0 39 26 1 1 0 0 0 39 44 1 0 0 0 0 39 62 1 0 0 0 0 40 27 1 1 0 0 0 40 51 1 0 0 0 0 40 64 1 0 0 0 0 41 29 1 1 0 0 0 41 52 1 0 0 0 0 41 63 1 0 0 0 0 42 57 1 6 0 0 0 42 68 1 0 0 0 0 43 28 1 1 0 0 0 43 56 1 0 0 0 0 43 67 1 0 0 0 0 44 70 1 6 0 0 0 45 60 2 0 0 0 0 45 71 1 0 0 0 0 46 65 2 3 0 0 0 46 72 1 0 0 0 0 47 53 1 6 0 0 0 47 65 1 0 0 0 0 48 33 1 1 0 0 0 48 58 1 0 0 0 0 48 66 1 0 0 0 0 49 34 1 1 0 0 0 49 54 1 0 0 0 0 49 83 1 0 0 0 0 50 35 1 6 0 0 0 50 59 1 0 0 0 0 50 84 1 0 0 0 0 51 63 2 3 0 0 0 51 73 1 0 0 0 0 52 62 2 3 0 0 0 52 74 1 0 0 0 0 53 61 2 3 0 0 0 53 75 1 0 0 0 0 54 64 2 3 0 0 0 54 76 1 0 0 0 0 55 67 1 0 0 0 0 55 77 2 0 0 0 0 56 68 1 0 0 0 0 56 78 2 0 0 0 0 57 79 2 0 0 0 0 57 82 1 0 0 0 0 58 80 2 0 0 0 0 58 84 1 0 0 0 0 59 81 2 0 0 0 0 59 83 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	1187.71
Volume:	1214.611
LogP:	2.662
LogD:	2.125
LogS:	-3.425
# Rotatable Bonds:	42
TPSA:	358.79
# H-Bond Aceptor:	25
# H-Bond Donor:	9
# Rings:	2
# Heavy Atoms:	25

MedChem Properties

QED Drug-Likeness Score:	0.021
Synthetic Accessibility Score:	6.445
Fsp3:	0.712
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.137
MDCK Permeability:	0.00022013775014784187
Pgp-inhibitor:	1.0
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.525
20% Bioavailability (F20%):	0.009
30% Bioavailability (F30%):	0.346

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.047
Plasma Protein Binding (PPB):	67.98065185546875%
Volume Distribution (VD):	0.583
Pgp-substrate:	23.161476135253906%

ADMET: Metabolism

CYP1A2-inhibitor:	0.0
CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.019
CYP2C19-substrate:	0.048
CYP2C9-inhibitor:	0.016
CYP2C9-substrate:	0.025
CYP2D6-inhibitor:	0.035
CYP2D6-substrate:	0.053
CYP3A4-inhibitor:	0.17
CYP3A4-substrate:	0.237

ADMET: Excretion

Clearance (CL):	6.78
Half-life (T1/2):	0.47

ADMET: Toxicity

hERG Blockers:	0.002
Human Hepatotoxicity (H-HT):	0.999
Drug-inuced Liver Injury (DILI):	0.96
AMES Toxicity:	0.004
Rat Oral Acute Toxicity:	0.012
Maximum Recommended Daily Dose:	0.624
Skin Sensitization:	0.091
Carcinogencity:	0.036
Eye Corrosion:	0.003
Eye Irritation:	0.003
Respiratory Toxicity:	0.646

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC197743

Natural Product ID:	NPC197743
*Common Name:**	Grassystatin B
IUPAC Name:	methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-2-[[(3S,4S)-4-[[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[(2S)-2-[(2S)-2-(dimethylamino)-3-methylbutanoyl]oxy-3-methylbutanoyl]oxy-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-hydroxybutanoyl]amino]butanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate
Synonyms:
Standard InCHIKey:	ICOVQVRWYNMTQP-UXVOKYIZSA-N
Standard InCHI:	InChI=1S/C59H97N9O16/c1-17-38(55(77)67(15)43(28-37-22-19-18-20-23-37)56(78)68-25-21-24-42(68)57(79)82-16)61-53(75)47(36(12)69)65-46(72)30-44(70)39(26-31(2)3)62-52(74)41(29-45(60)71)63-51(73)40(27-32(4)5)64-54(76)49(34(8)9)83-59(81)50(35(10)11)84-58(80)48(33(6)7)66(13)14/h18-20,22-23,31-36,38-44,47-50,69-70H,17,21,24-30H2,1-16H3,(H2,60,71)(H,61,75)(H,62,74)(H,63,73)(H,64,76)(H,65,72)/t36-,38+,39+,40+,41+,42+,43-,44+,47+,48+,49-,50+/m1/s1
SMILES:	CC[C@@H](C(=O)N(C)[C@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)OC)N=C([C@H]([C@@H](C)O)N=C(C[C@@H]([C@H](CC(C)C)N=C([C@H](CC(=N)O)N=C([C@H](CC(C)C)N=C([C@@H](C(C)C)OC(=O)[C@H](C(C)C)OC(=O)[C@H](C(C)C)N(C)C)O)O)O)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL568553
PubChem CID:	44253976
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33098	cyanobacteria	Phylum	n.a.	Bacteria	n.a.	n.a.	n.a.	PMID[19715320]
NPO33098	cyanobacteria	Phylum	n.a.	Bacteria	n.a.	n.a.	n.a.	PMID[23350733]
NPO40680	Marine cyanobacterium from Guam	Strain	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[29087712]

☑ 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	NP ID	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	6
Others	2

Activity Type	# Activity
Individual Protein	6
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6510	Individual Protein	Cathepsin E	Homo sapiens	IC50	=	0.354	nM	PMID[548787]
NPT6515	Individual Protein	ADAM9	Homo sapiens	IC50	=	85500.0	nM	PMID[548787]
NPT6299	Individual Protein	ADAM10	Homo sapiens	IC50	=	87200.0	nM	PMID[548787]
NPT3910	Individual Protein	ADAM17	Homo sapiens	IC50	=	2230.0	nM	PMID[548787]
NPT1547	Individual Protein	Cathepsin D	Homo sapiens	IC50	=	7.3	nM	PMID[548788]
NPT6510	Individual Protein	Cathepsin E	Homo sapiens	IC50	=	0.4	nM	PMID[548788]
NPT2	Others	Unspecified		Ratio IC50	=	20.0	n.a.	PMID[548787]
NPT2	Others	Unspecified		Ratio IC50	=	18.3	n.a.	PMID[548788]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC197743 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	149
0.1-0.2	729
0.2-0.3	2949
0.3-0.4	18283
0.4-0.5	16566
0.5-0.6	3092
0.6-0.7	589
0.7-0.8	239
0.8-0.85	55
0.85-0.9	32
0.9-0.95	9
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC297145
0.9379	High Similarity	NPC2501
0.931	High Similarity	NPC471821
0.931	High Similarity	NPC471820
0.9189	High Similarity	NPC122590
0.9034	High Similarity	NPC52748
0.8993	High Similarity	NPC162104
0.8973	High Similarity	NPC5620
0.8897	High Similarity	NPC269398
0.8897	High Similarity	NPC263493
0.8776	High Similarity	NPC476978
0.8759	High Similarity	NPC476133
0.8759	High Similarity	NPC92784
0.8759	High Similarity	NPC470884
0.8759	High Similarity	NPC98424
0.8759	High Similarity	NPC178662
0.8733	High Similarity	NPC129666
0.8716	High Similarity	NPC209509
0.8699	High Similarity	NPC268841
0.8699	High Similarity	NPC307357
0.8699	High Similarity	NPC46098
0.869	High Similarity	NPC68865
0.869	High Similarity	NPC471264
0.869	High Similarity	NPC471265
0.8634	High Similarity	NPC477462
0.86	High Similarity	NPC329761
0.86	High Similarity	NPC145113
0.86	High Similarity	NPC225648
0.8543	High Similarity	NPC240848
0.8533	High Similarity	NPC262077
0.8467	Intermediate Similarity	NPC315266
0.8456	Intermediate Similarity	NPC139326
0.8456	Intermediate Similarity	NPC161069
0.8446	Intermediate Similarity	NPC163392
0.8446	Intermediate Similarity	NPC239762
0.8355	Intermediate Similarity	NPC135121
0.8354	Intermediate Similarity	NPC471527
0.8333	Intermediate Similarity	NPC197682
0.8333	Intermediate Similarity	NPC176226
0.8312	Intermediate Similarity	NPC7817
0.8312	Intermediate Similarity	NPC475168
0.8293	Intermediate Similarity	NPC26108
0.8291	Intermediate Similarity	NPC62104
0.8291	Intermediate Similarity	NPC1390
0.8267	Intermediate Similarity	NPC168113
0.8235	Intermediate Similarity	NPC138775
0.8224	Intermediate Similarity	NPC201244
0.8224	Intermediate Similarity	NPC477217
0.82	Intermediate Similarity	NPC476259
0.8188	Intermediate Similarity	NPC127741
0.817	Intermediate Similarity	NPC314358
0.8153	Intermediate Similarity	NPC470902
0.8137	Intermediate Similarity	NPC471053
0.8137	Intermediate Similarity	NPC471052
0.8137	Intermediate Similarity	NPC471051
0.8105	Intermediate Similarity	NPC313867
0.8105	Intermediate Similarity	NPC316008
0.8098	Intermediate Similarity	NPC63040
0.8095	Intermediate Similarity	NPC130309
0.8089	Intermediate Similarity	NPC473341
0.8086	Intermediate Similarity	NPC5719
0.8086	Intermediate Similarity	NPC22883
0.8086	Intermediate Similarity	NPC217804
0.8086	Intermediate Similarity	NPC210377
0.8072	Intermediate Similarity	NPC471165
0.8054	Intermediate Similarity	NPC248283
0.8039	Intermediate Similarity	NPC315283
0.8039	Intermediate Similarity	NPC314388
0.8037	Intermediate Similarity	NPC15068
0.8014	Intermediate Similarity	NPC319766
0.8012	Intermediate Similarity	NPC469901
0.8	Intermediate Similarity	NPC475204
0.8	Intermediate Similarity	NPC475123
0.7987	Intermediate Similarity	NPC287401
0.7986	Intermediate Similarity	NPC46427
0.7986	Intermediate Similarity	NPC6975
0.7949	Intermediate Similarity	NPC105717
0.7917	Intermediate Similarity	NPC252878
0.7917	Intermediate Similarity	NPC50016
0.7857	Intermediate Similarity	NPC318930
0.7857	Intermediate Similarity	NPC317362
0.7847	Intermediate Similarity	NPC202521
0.7811	Intermediate Similarity	NPC469900
0.7798	Intermediate Similarity	NPC137627
0.7778	Intermediate Similarity	NPC200964
0.7778	Intermediate Similarity	NPC476990
0.775	Intermediate Similarity	NPC286551
0.7744	Intermediate Similarity	NPC73655
0.7742	Intermediate Similarity	NPC77905
0.7733	Intermediate Similarity	NPC255447
0.7725	Intermediate Similarity	NPC473000
0.7719	Intermediate Similarity	NPC475421
0.7701	Intermediate Similarity	NPC299806
0.7697	Intermediate Similarity	NPC141050
0.7692	Intermediate Similarity	NPC306804
0.7692	Intermediate Similarity	NPC273755
0.7679	Intermediate Similarity	NPC196091
0.7677	Intermediate Similarity	NPC469427
0.7677	Intermediate Similarity	NPC469426
0.7651	Intermediate Similarity	NPC63931
0.7647	Intermediate Similarity	NPC326407
0.7647	Intermediate Similarity	NPC317725
0.7643	Intermediate Similarity	NPC322878
0.7639	Intermediate Similarity	NPC237420
0.7639	Intermediate Similarity	NPC310467
0.7635	Intermediate Similarity	NPC101719
0.7633	Intermediate Similarity	NPC89831
0.7622	Intermediate Similarity	NPC469898
0.7619	Intermediate Similarity	NPC474082
0.7619	Intermediate Similarity	NPC175726
0.7616	Intermediate Similarity	NPC45037
0.76	Intermediate Similarity	NPC473322
0.7588	Intermediate Similarity	NPC248670
0.7586	Intermediate Similarity	NPC167763
0.7586	Intermediate Similarity	NPC470903
0.7586	Intermediate Similarity	NPC470112
0.7578	Intermediate Similarity	NPC300443
0.7574	Intermediate Similarity	NPC46009
0.7569	Intermediate Similarity	NPC169328
0.7568	Intermediate Similarity	NPC222466
0.7544	Intermediate Similarity	NPC473354
0.7543	Intermediate Similarity	NPC471050
0.7543	Intermediate Similarity	NPC471048
0.7543	Intermediate Similarity	NPC471049
0.7533	Intermediate Similarity	NPC89923
0.7533	Intermediate Similarity	NPC152850
0.7533	Intermediate Similarity	NPC105114
0.7533	Intermediate Similarity	NPC71933
0.7533	Intermediate Similarity	NPC239990
0.7529	Intermediate Similarity	NPC328494
0.7514	Intermediate Similarity	NPC269750
0.7514	Intermediate Similarity	NPC194671
0.7483	Intermediate Similarity	NPC111428
0.7471	Intermediate Similarity	NPC40234
0.7467	Intermediate Similarity	NPC136453
0.7455	Intermediate Similarity	NPC324850
0.7453	Intermediate Similarity	NPC283783
0.7443	Intermediate Similarity	NPC294951
0.7442	Intermediate Similarity	NPC476227
0.7442	Intermediate Similarity	NPC279871
0.7439	Intermediate Similarity	NPC469903
0.7436	Intermediate Similarity	NPC132636
0.7434	Intermediate Similarity	NPC300315
0.7432	Intermediate Similarity	NPC477550
0.7432	Intermediate Similarity	NPC477552
0.7429	Intermediate Similarity	NPC476321
0.7415	Intermediate Similarity	NPC478016
0.7415	Intermediate Similarity	NPC478015
0.7415	Intermediate Similarity	NPC478014
0.7386	Intermediate Similarity	NPC157311
0.7386	Intermediate Similarity	NPC471526
0.7374	Intermediate Similarity	NPC102959
0.7365	Intermediate Similarity	NPC469902
0.7353	Intermediate Similarity	NPC107938
0.7353	Intermediate Similarity	NPC294516
0.7351	Intermediate Similarity	NPC477551
0.7341	Intermediate Similarity	NPC155506
0.7341	Intermediate Similarity	NPC159767
0.7338	Intermediate Similarity	NPC44805
0.7338	Intermediate Similarity	NPC8761
0.7338	Intermediate Similarity	NPC246079
0.7337	Intermediate Similarity	NPC472923
0.7333	Intermediate Similarity	NPC61332
0.7333	Intermediate Similarity	NPC163961
0.7333	Intermediate Similarity	NPC240130
0.7333	Intermediate Similarity	NPC473305
0.7333	Intermediate Similarity	NPC60516
0.7326	Intermediate Similarity	NPC230611
0.732	Intermediate Similarity	NPC200589
0.7318	Intermediate Similarity	NPC94862
0.7317	Intermediate Similarity	NPC262166
0.7308	Intermediate Similarity	NPC302715
0.7305	Intermediate Similarity	NPC24617
0.7294	Intermediate Similarity	NPC61004
0.7285	Intermediate Similarity	NPC47667
0.7279	Intermediate Similarity	NPC470546
0.7279	Intermediate Similarity	NPC314992
0.7267	Intermediate Similarity	NPC473693
0.7267	Intermediate Similarity	NPC35996
0.7267	Intermediate Similarity	NPC471568
0.7262	Intermediate Similarity	NPC114806
0.7261	Intermediate Similarity	NPC43755
0.7251	Intermediate Similarity	NPC473502
0.7241	Intermediate Similarity	NPC473402
0.7232	Intermediate Similarity	NPC473404
0.7229	Intermediate Similarity	NPC476268
0.7229	Intermediate Similarity	NPC244509
0.7213	Intermediate Similarity	NPC65714
0.7212	Intermediate Similarity	NPC56685
0.7211	Intermediate Similarity	NPC470545
0.7209	Intermediate Similarity	NPC186617
0.7181	Intermediate Similarity	NPC190663
0.7181	Intermediate Similarity	NPC45777
0.7181	Intermediate Similarity	NPC477061
0.7175	Intermediate Similarity	NPC472999
0.7159	Intermediate Similarity	NPC473001
0.7143	Intermediate Similarity	NPC14672
0.7143	Intermediate Similarity	NPC470544
0.7143	Intermediate Similarity	NPC285926
0.7143	Intermediate Similarity	NPC2265

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC197743 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	107
0.1-0.2	301
0.2-0.3	659
0.3-0.4	2537
0.4-0.5	3782
0.5-0.6	1445
0.6-0.7	272
0.7-0.8	45
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8435	Intermediate Similarity	NPD8172	Phase 2
0.8435	Intermediate Similarity	NPD8173	Phase 2
0.8	Intermediate Similarity	NPD7113	Clinical (unspecified phase)
0.7862	Intermediate Similarity	NPD2584	Suspended
0.7838	Intermediate Similarity	NPD4177	Approved
0.7838	Intermediate Similarity	NPD4175	Approved
0.7826	Intermediate Similarity	NPD8417	Discontinued
0.7815	Intermediate Similarity	NPD8416	Discontinued
0.7712	Intermediate Similarity	NPD5725	Approved
0.7712	Intermediate Similarity	NPD6073	Approved
0.7662	Intermediate Similarity	NPD6852	Discontinued
0.7658	Intermediate Similarity	NPD8323	Discontinued
0.7632	Intermediate Similarity	NPD5747	Discontinued
0.7628	Intermediate Similarity	NPD8076	Discontinued
0.7578	Intermediate Similarity	NPD7613	Discontinued
0.7561	Intermediate Similarity	NPD7118	Clinical (unspecified phase)
0.7533	Intermediate Similarity	NPD5339	Clinical (unspecified phase)
0.7532	Intermediate Similarity	NPD8643	Discontinued
0.7516	Intermediate Similarity	NPD7634	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD3072	Approved
0.75	Intermediate Similarity	NPD3073	Approved
0.75	Intermediate Similarity	NPD3071	Approved
0.7467	Intermediate Similarity	NPD2585	Clinical (unspecified phase)
0.7436	Intermediate Similarity	NPD6901	Phase 3
0.7432	Intermediate Similarity	NPD4762	Approved
0.7432	Intermediate Similarity	NPD4761	Approved
0.7372	Intermediate Similarity	NPD4782	Clinical (unspecified phase)
0.7355	Intermediate Similarity	NPD4153	Approved
0.7349	Intermediate Similarity	NPD7749	Clinical (unspecified phase)
0.7346	Intermediate Similarity	NPD7892	Clinical (unspecified phase)
0.732	Intermediate Similarity	NPD4676	Approved
0.732	Intermediate Similarity	NPD4125	Approved
0.732	Intermediate Similarity	NPD5263	Approved
0.7279	Intermediate Similarity	NPD2218	Phase 2
0.7279	Intermediate Similarity	NPD2217	Approved
0.7273	Intermediate Similarity	NPD4738	Phase 2
0.7273	Intermediate Similarity	NPD4794	Discontinued
0.7205	Intermediate Similarity	NPD5265	Approved
0.7205	Intermediate Similarity	NPD6860	Clinical (unspecified phase)
0.7205	Intermediate Similarity	NPD5264	Approved
0.72	Intermediate Similarity	NPD4706	Clinical (unspecified phase)
0.717	Intermediate Similarity	NPD7728	Clinical (unspecified phase)
0.716	Intermediate Similarity	NPD4557	Approved
0.7143	Intermediate Similarity	NPD3626	Phase 3
0.7134	Intermediate Similarity	NPD6631	Clinical (unspecified phase)
0.7134	Intermediate Similarity	NPD6088	Approved
0.7134	Intermediate Similarity	NPD5296	Approved
0.7134	Intermediate Similarity	NPD8265	Approved
0.7134	Intermediate Similarity	NPD4791	Clinical (unspecified phase)
0.7134	Intermediate Similarity	NPD6623	Phase 3
0.7115	Intermediate Similarity	NPD1329	Clinical (unspecified phase)
0.7115	Intermediate Similarity	NPD1330	Phase 2
0.7097	Intermediate Similarity	NPD7979	Clinical (unspecified phase)
0.7083	Intermediate Similarity	NPD7267	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD3608	Clinical (unspecified phase)
0.7051	Intermediate Similarity	NPD6919	Clinical (unspecified phase)
0.7032	Intermediate Similarity	NPD3040	Approved
0.7019	Intermediate Similarity	NPD7511	Approved
0.7019	Intermediate Similarity	NPD7512	Approved
0.7006	Intermediate Similarity	NPD4619	Approved
0.7006	Intermediate Similarity	NPD4621	Approved
0.7006	Intermediate Similarity	NPD3632	Clinical (unspecified phase)
0.6994	Remote Similarity	NPD8303	Discontinued
0.6989	Remote Similarity	NPD8124	Phase 3
0.6989	Remote Similarity	NPD7964	Clinical (unspecified phase)
0.6989	Remote Similarity	NPD8126	Clinical (unspecified phase)
0.6989	Remote Similarity	NPD7965	Phase 2
0.6987	Remote Similarity	NPD2613	Approved
0.6975	Remote Similarity	NPD4152	Approved
0.6962	Remote Similarity	NPD3090	Approved
0.6962	Remote Similarity	NPD3614	Approved
0.6962	Remote Similarity	NPD3088	Approved
0.6962	Remote Similarity	NPD3089	Approved
0.6962	Remote Similarity	NPD4745	Approved
0.6962	Remote Similarity	NPD2572	Clinical (unspecified phase)
0.6962	Remote Similarity	NPD2571	Approved
0.6962	Remote Similarity	NPD2574	Discontinued
0.6962	Remote Similarity	NPD2573	Approved
0.6962	Remote Similarity	NPD3615	Approved
0.6962	Remote Similarity	NPD3616	Approved
0.6962	Remote Similarity	NPD3087	Approved
0.6962	Remote Similarity	NPD2570	Approved
0.6962	Remote Similarity	NPD2566	Approved
0.6962	Remote Similarity	NPD4746	Phase 3
0.6959	Remote Similarity	NPD1348	Approved
0.6951	Remote Similarity	NPD2575	Approved
0.6951	Remote Similarity	NPD6676	Phase 2
0.6933	Remote Similarity	NPD6119	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD5341	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD3661	Approved
0.6923	Remote Similarity	NPD3662	Phase 3
0.6923	Remote Similarity	NPD5759	Approved
0.6923	Remote Similarity	NPD3664	Approved
0.6923	Remote Similarity	NPD3663	Approved
0.6918	Remote Similarity	NPD5323	Approved
0.6903	Remote Similarity	NPD2159	Approved
0.6903	Remote Similarity	NPD2627	Approved
0.6903	Remote Similarity	NPD2626	Approved
0.6903	Remote Similarity	NPD2628	Approved
0.6903	Remote Similarity	NPD2160	Approved
0.6903	Remote Similarity	NPD2625	Approved
0.6894	Remote Similarity	NPD6294	Approved
0.6894	Remote Similarity	NPD6295	Approved
0.6894	Remote Similarity	NPD4126	Approved
0.6887	Remote Similarity	NPD4504	Clinical (unspecified phase)
0.6883	Remote Similarity	NPD4677	Discontinued
0.6875	Remote Similarity	NPD4684	Phase 3
0.6875	Remote Similarity	NPD4686	Approved
0.6875	Remote Similarity	NPD4685	Phase 3
0.6864	Remote Similarity	NPD4648	Approved
0.6864	Remote Similarity	NPD8315	Phase 1
0.6864	Remote Similarity	NPD4646	Approved
0.6864	Remote Similarity	NPD4647	Approved
0.6863	Remote Similarity	NPD4215	Approved
0.6863	Remote Similarity	NPD4216	Approved
0.6863	Remote Similarity	NPD4218	Approved
0.6863	Remote Similarity	NPD2611	Approved
0.6863	Remote Similarity	NPD3131	Approved
0.6863	Remote Similarity	NPD4217	Approved
0.6863	Remote Similarity	NPD2610	Approved
0.6863	Remote Similarity	NPD3132	Approved
0.6863	Remote Similarity	NPD2609	Approved
0.6863	Remote Similarity	NPD2612	Approved
0.6863	Remote Similarity	NPD2608	Approved
0.6859	Remote Similarity	NPD3588	Discontinued
0.6859	Remote Similarity	NPD3604	Clinical (unspecified phase)
0.6832	Remote Similarity	NPD7510	Approved
0.6829	Remote Similarity	NPD6681	Discovery
0.6829	Remote Similarity	NPD2437	Approved
0.6829	Remote Similarity	NPD2436	Approved
0.6816	Remote Similarity	NPD8022	Clinical (unspecified phase)
0.6815	Remote Similarity	NPD5204	Approved
0.6792	Remote Similarity	NPD2078	Clinical (unspecified phase)
0.6792	Remote Similarity	NPD5299	Approved
0.6768	Remote Similarity	NPD7720	Phase 2
0.6768	Remote Similarity	NPD2087	Approved
0.6768	Remote Similarity	NPD2088	Approved
0.6766	Remote Similarity	NPD8290	Clinical (unspecified phase)
0.6765	Remote Similarity	NPD6670	Clinical (unspecified phase)
0.6763	Remote Similarity	NPD7599	Phase 2
0.6752	Remote Similarity	NPD4151	Approved
0.6748	Remote Similarity	NPD5301	Clinical (unspecified phase)
0.6747	Remote Similarity	NPD5298	Clinical (unspecified phase)
0.6746	Remote Similarity	NPD5229	Approved
0.6746	Remote Similarity	NPD5230	Approved
0.6731	Remote Similarity	NPD6792	Phase 3
0.6731	Remote Similarity	NPD3125	Approved
0.6686	Remote Similarity	NPD8351	Phase 2
0.6686	Remote Similarity	NPD4185	Clinical (unspecified phase)
0.6685	Remote Similarity	NPD7608	Discontinued
0.6685	Remote Similarity	NPD5681	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD3908	Approved
0.6667	Remote Similarity	NPD747	Discontinued
0.6667	Remote Similarity	NPD8103	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD4508	Discontinued
0.6667	Remote Similarity	NPD7978	Discontinued
0.6667	Remote Similarity	NPD2022	Approved
0.6667	Remote Similarity	NPD5981	Approved
0.6647	Remote Similarity	NPD1663	Discontinued
0.6647	Remote Similarity	NPD6078	Clinical (unspecified phase)
0.6646	Remote Similarity	NPD3480	Approved
0.6629	Remote Similarity	NPD7600	Phase 2
0.6629	Remote Similarity	NPD7080	Clinical (unspecified phase)
0.6625	Remote Similarity	NPD2047	Approved
0.6625	Remote Similarity	NPD2046	Approved
0.6625	Remote Similarity	NPD2048	Approved
0.6625	Remote Similarity	NPD2049	Clinical (unspecified phase)
0.6625	Remote Similarity	NPD2043	Approved
0.6625	Remote Similarity	NPD2045	Approved
0.6625	Remote Similarity	NPD2044	Approved
0.6625	Remote Similarity	NPD2051	Approved
0.6625	Remote Similarity	NPD2050	Clinical (unspecified phase)
0.6625	Remote Similarity	NPD21	Approved
0.6624	Remote Similarity	NPD5367	Discontinued
0.6584	Remote Similarity	NPD5581	Approved
0.6564	Remote Similarity	NPD4757	Clinical (unspecified phase)
0.6562	Remote Similarity	NPD4617	Approved
0.6562	Remote Similarity	NPD4620	Approved
0.6562	Remote Similarity	NPD5201	Approved
0.6562	Remote Similarity	NPD5203	Approved
0.6562	Remote Similarity	NPD5202	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD7105	Phase 1
0.655	Remote Similarity	NPD5638	Approved
0.6543	Remote Similarity	NPD3561	Clinical (unspecified phase)
0.6538	Remote Similarity	NPD4807	Approved
0.6538	Remote Similarity	NPD4806	Approved
0.6536	Remote Similarity	NPD7484	Phase 3
0.6536	Remote Similarity	NPD7485	Phase 3
0.6516	Remote Similarity	NPD7342	Discontinued
0.651	Remote Similarity	NPD3642	Approved
0.651	Remote Similarity	NPD3643	Approved
0.651	Remote Similarity	NPD3644	Approved
0.6509	Remote Similarity	NPD7602	Clinical (unspecified phase)
0.6509	Remote Similarity	NPD6552	Clinical (unspecified phase)
0.6506	Remote Similarity	NPD4173	Approved
0.6506	Remote Similarity	NPD4172	Approved
0.6503	Remote Similarity	NPD6311	Approved
0.6503	Remote Similarity	NPD5121	Approved
0.6503	Remote Similarity	NPD5119	Approved
0.6503	Remote Similarity	NPD6309	Approved

Bioactivity similarity: Similar Natural Products in NPASS

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