NPASS Compound

Natural Product: NPC45324

Natural Product ID	NPC45324
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Dehydrotumulosic Acid
IUPAC Name	(2R)-2-[(3S,5R,10S,13R,14R,16R,17R)-3,16-dihydroxy-4,4,10,13,14-pentamethyl-2,3,5,6,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-6-methyl-5-methylideneheptanoic acid
Synonyms	Dehydrotumulosic Acid
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL517584
PubChem CID	15225964
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001445] Bile acids, alcohols and derivatives [CHEMONTID:0002194] Hydroxy bile acids, alcohols and derivatives [CHEMONTID:0000516] Dihydroxy bile acids, alcohols and derivatives

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 83 86 0 0 0 0 0 0 0 0999 V2000 -7.3922 1.6304 -1.0681 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6352 0.6844 -0.1837 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6168 0.0823 0.8150 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1137 -0.4426 -0.9896 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3041 -0.4454 -2.2974 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4300 -1.5480 -0.3453 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2283 -1.3343 0.4776 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0388 -0.7838 -0.2038 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8481 -0.6563 0.7373 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5088 -2.0219 1.3394 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0149 -2.0439 1.5702 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3869 -0.6364 1.2775 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0405 0.2161 2.4651 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7722 -0.4346 0.9069 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7521 -0.9130 1.6343 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1894 -0.7366 1.3027 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3332 0.4995 0.4424 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7366 0.9101 0.2128 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2586 1.4952 1.5328 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6731 -0.1683 -0.2003 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7973 2.0207 -0.7947 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1168 1.6858 -2.0919 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6638 1.4178 -1.7984 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4935 0.3092 -0.7790 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6971 -1.0492 -1.4202 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0647 0.3247 -0.3128 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1282 0.9790 -0.9590 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3077 0.9819 -0.4746 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5537 -0.3582 0.0810 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2065 -1.4129 -0.9548 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1470 2.2867 -1.1042 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2103 -2.0932 2.5418 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2746 0.5888 -0.7046 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1452 1.5458 0.1363 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6143 0.9628 -1.9786 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2663 1.1647 -1.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7922 2.1491 -1.8169 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8618 2.4550 -0.4495 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8504 1.2507 0.3156 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9604 0.9112 1.4607 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4436 -0.3633 0.2305 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0519 -0.6905 1.3781 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8329 0.3675 -2.7555 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9499 -1.2377 -2.9484 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1955 -2.2058 0.2223 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1128 -2.2767 -1.1759 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9662 -2.3751 0.8891 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5195 -0.7266 1.3876 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7487 -1.4724 -1.0199 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0602 0.0409 1.5426 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8321 -2.8623 0.7317 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1768 -2.2422 2.6537 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5081 -2.7991 0.9676 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8743 0.3708 3.0766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4614 1.1889 2.1523 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7508 -0.3397 3.1250 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5016 -1.4684 2.5276 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5365 -1.6519 0.8280 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7328 -0.5342 2.2488 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8399 1.3272 1.0363 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1749 2.0632 1.2664 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5320 0.6947 2.2251 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5430 2.2341 1.9448 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8269 -0.1605 -1.3191 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4122 -1.1782 0.1723 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6779 0.0600 0.2134 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3816 2.9609 -0.4080 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1499 2.6069 -2.7208 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6134 0.8630 -2.6403 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2395 2.3518 -1.3763 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1631 1.0911 -2.7319 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2145 -1.8583 -0.8347 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7444 -1.3252 -1.5464 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2278 -1.0730 -2.4226 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3800 1.5207 -1.8436 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9617 1.1274 -1.3696 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4684 1.8217 0.2109 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2533 -0.9498 -1.9599 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8833 -2.2742 -0.9596 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8177 -1.7879 -0.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1448 2.8362 -1.9277 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4853 -3.0279 2.7346 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4321 1.8808 -2.3855 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 12 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 18 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 6 24 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 29 30 1 6 21 31 1 0 10 32 1 0 8 33 1 0 33 34 2 0 33 35 1 0 29 9 1 0 29 12 1 0 26 14 1 0 24 17 1 0 1 36 1 0 1 37 1 0 1 38 1 0 2 39 1 0 3 40 1 0 3 41 1 0 3 42 1 0 5 43 1 0 5 44 1 0 6 45 1 0 6 46 1 0 7 47 1 0 7 48 1 0 8 49 1 6 9 50 1 1 10 51 1 6 11 52 1 0 11 53 1 0 13 54 1 0 13 55 1 0 13 56 1 0 15 57 1 0 16 58 1 0 16 59 1 0 17 60 1 1 19 61 1 0 19 62 1 0 19 63 1 0 20 64 1 0 20 65 1 0 20 66 1 0 21 67 1 1 22 68 1 0 22 69 1 0 23 70 1 0 23 71 1 0 25 72 1 0 25 73 1 0 25 74 1 0 27 75 1 0 28 76 1 0 28 77 1 0 30 78 1 0 30 79 1 0 30 80 1 0 31 81 1 0 32 82 1 0 35 83 1 0 M END

Standard InCHIKey	LADJWZMBZBVBSB-YEXRKOARSA-N
Standard InCHI	InChI=1S/C31H48O4/c1-18(2)19(3)9-10-20(27(34)35)26-23(32)17-31(8)22-11-12-24-28(4,5)25(33)14-15-29(24,6)21(22)13-16-30(26,31)7/h11,13,18,20,23-26,32-33H,3,9-10,12,14-17H2,1-2,4-8H3,(H,34,35)/t20-,23-,24+,25+,26+,29-,30-,31+/m1/s1
SMILES	CC(C)C(=C)CC[C@H]([C@H]1[C@@H](C[C@@]2(C)C3=CC[C@H]4C(C)(C)[C@H](CC[C@]4(C)C3=CC[C@]12C)O)O)C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	484.36	Volume:	535.121 ? Van der Waals volume.
Dense:	0.905	LogP:	4.317 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.439 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.225 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	22.0
TPSA:	77.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.374	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.14	Fsp³:	0.774
MCE-18:	84.073 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.747	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.073 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.354	Promiscuous compounds:	0.081

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.411	MDCK Permeability:	-4.964
Pgp-inhibitor:	0.001	Pgp-substrate:	0.022
PAMPA:	0.991 ? 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%):	0.043	30% Bioavailability (F30%):	0.016
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.021	MRP1:	0.994
Plasma Protein Binding (PPB):	89.696%	Volume Distribution (VD):	-0.262
Fu:	8.755% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.182
BSEP inhibitor:	0.977

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.011
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.01
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.143 ? 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):

7.162

Half-life (T1/2):

1.082

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.083
Human Hepatotoxicity (H-HT):	0.442	Drug-induced Liver Injury (DILI):	0.045
AMES Toxicity:	0.155	Rat Oral Acute Toxicity:	0.227
Maximum Recommended Daily Dose:	0.271	Skin Sensitization:	0.911
Carcinogencity:	0.473	Eye Corrosion:	0.009
Eye Irritation:	0.473	Respiratory Toxicity:	0.52
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.744
Hematotoxicity:	0.274	Drug-induced Nephrotoxicity:	0.688
Genotoxicity:	0.37	RPMI-8226 Immunitoxicity:	0.105
A549 Cytotoxicity:	0.039	Hek293 Cytotoxicity:	0.088
BCF:	0.783 ? 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:	3.559 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.284 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.42 ? 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
NPO23577	Wolfiporia cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11975480]
NPO23577	Wolfiporia cocos	Species	Coriolaceae	Eukaryota	epidermis of the sclerotia	n.a.	n.a.	PMID[19746919]
NPO30645	Poria cocos	Species	Coriolaceae	Eukaryota	n.a.	sclerotium	n.a.	PMID[21250700]
NPO23577	Wolfiporia cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27808511]
NPO23577	Wolfiporia cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8984162]
NPO10608	Exodermis poria	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23577	Wolfiporia cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30645	Poria cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30645	Poria cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10608	Exodermis poria	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO10608	Exodermis poria	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO23577	Wolfiporia cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO30645	Poria cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23577	Wolfiporia cocos	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23577	Wolfiporia cocos	Species	Coriolaceae	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

Activity Type	# Activity
IC50	5
Inhibition	1
Activity	5

Activity Type	# Activity
Individual protein	2
Cell line	5
Others	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2586	Individual protein	Phospholipase A2, acidic	Naja naja	IC50	=	845000.0	nM	PMID[8984162]
NPT2586	Individual protein	Phospholipase A2, acidic	Naja naja	Inhibition	=	58.6	%	PMID[8984162]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT80	Cell line	Raji	Homo sapiens	Activity	=	70.0	%	PMID[11975480]
NPT111	Cell line	K562	Homo sapiens	IC50	>	40000.0	nM	PMID[27808511]
NPT116	Cell line	HL-60	Homo sapiens	IC50	>	40000.0	nM	PMID[27808511]
NPT404	Cell line	CCRF-CEM	Homo sapiens	IC50	>	40000.0	nM	PMID[27808511]
NPT112	Cell line	MOLT-4	Homo sapiens	IC50	>	40000.0	nM	PMID[27808511]
NPT2	Others	Unspecified	n.a.	Activity	=	0.0	%	PMID[11975480]
NPT2	Others	Unspecified	n.a.	Activity	=	22.7	%	PMID[11975480]
NPT2	Others	Unspecified	n.a.	Activity	=	64.9	%	PMID[11975480]
NPT2	Others	Unspecified	n.a.	Activity	=	90.5	%	PMID[11975480]

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 NPC45324 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	18508
0.1-0.2	27104
0.2-0.3	3846
0.3-0.4	305
0.4-0.5	41
0.5-0.6	23
0.6-0.7	7
0.7-0.8	0
0.8-0.85	4
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC162001
0.8548	High Similarity	NPC186810
0.8413	Intermediate Similarity	NPC484967
0.8125	Intermediate Similarity	NPC484968
0.8065	Intermediate Similarity	NPC222845
0.8065	Intermediate Similarity	NPC296577
0.7692	Intermediate Similarity	NPC484975
0.7692	Intermediate Similarity	NPC48647
0.7692	Intermediate Similarity	NPC321301
0.7538	Intermediate Similarity	NPC77168
0.75	Intermediate Similarity	NPC288464
0.75	Intermediate Similarity	NPC477813
0.75	Intermediate Similarity	NPC607198
0.7424	Intermediate Similarity	NPC477812
0.7353	Intermediate Similarity	NPC263347
0.7313	Intermediate Similarity	NPC152897
0.7015	Intermediate Similarity	NPC203035
0.6812	Remote Similarity	NPC123854
0.6618	Remote Similarity	NPC48866
0.6567	Remote Similarity	NPC23434
0.6301	Remote Similarity	NPC484969
0.625	Remote Similarity	NPC155676
0.6	Remote Similarity	NPC84271
0.6	Remote Similarity	NPC102414
0.5833	Remote Similarity	NPC66429
0.5811	Remote Similarity	NPC7165
0.5753	Remote Similarity	NPC469406
0.5753	Remote Similarity	NPC484966
0.5634	Remote Similarity	NPC484974
0.5616	Remote Similarity	NPC45269
0.56	Remote Similarity	NPC141401
0.5584	Remote Similarity	NPC469432
0.5556	Remote Similarity	NPC76895
0.5541	Remote Similarity	NPC214697
0.5479	Remote Similarity	NPC212948
0.5405	Remote Similarity	NPC484971
0.5405	Remote Similarity	NPC484970
0.5342	Remote Similarity	NPC247406
0.5294	Remote Similarity	NPC72507
0.5278	Remote Similarity	NPC55309
0.5278	Remote Similarity	NPC28252
0.5211	Remote Similarity	NPC201852
0.5211	Remote Similarity	NPC231310
0.52	Remote Similarity	NPC484976
0.5195	Remote Similarity	NPC184848
0.5067	Remote Similarity	NPC46281
0.5067	Remote Similarity	NPC69279

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC45324 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6162
0.1-0.2	2922
0.2-0.3	65
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
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
		NPD

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